|
| Publications of Virginia B Kraus :chronological combined listing:
%% Papers Published
@article{fds188644,
Author = {VB Kraus and B Burnett and J Coindreau and S Cottrell and D Eyre and M
Gendreau, J Gardiner and P Garnero and J Hardin and Y Henrotin and D
Heinegård, A Ko and LS Lohmander and G Matthews and J Menetski and R
Moskowitz, S Persiani and AR Poole and JC Rousseau and M Todman and OARSI FDA Osteoarthritis Biomarkers Working
Group},
Title = {Application of biomarkers in the development of drugs
intended for the treatment of osteoarthritis.},
Journal = {Osteoarthritis and cartilage / OARS, Osteoarthritis Research
Society},
Volume = {19},
Number = {5},
Pages = {515-42},
Year = {2011},
Month = {May},
ISSN = {1522-9653},
url = {http://dx.doi.org/10.1016/j.joca.2010.08.019},
Keywords = {Biological Markers • Clinical Trials as Topic •
Drug Discovery • Drug Monitoring • Humans •
Osteoarthritis • Specimen Handling • Treatment
Outcome • diagnosis • drug therapy* •
metabolism* • methods • methods*},
Abstract = {OBJECTIVE: Osteoarthritis (OA) is a chronic and slowly
progressive disease for which biomarkers may be able to
provide a more rapid indication of therapeutic responses to
therapy than is currently available; this could accelerate
and facilitate OA drug discovery and development programs.
The goal of this document is to provide a summary and guide
to the application of in vitro (biochemical and other
soluble) biomarkers in the development of drugs for OA and
to outline and stimulate a research agenda that will further
this goal. METHODS: The Biomarkers Working Group
representing experts in the field of OA biomarker research
from both academia and industry developed this consensus
document between 2007 and 2009 at the behest of the
Osteoarthritis Research Society International Federal Drug
Administration initiative (OARSI FDA initiative). RESULTS:
This document summarizes definitions and classification
systems for biomarkers, the current outcome measures used in
OA clinical trials, applications and potential utility of
biomarkers for development of OA therapeutics, the current
state of qualification of OA-related biomarkers, pathways
for biomarker qualification, critical needs to advance the
use of biomarkers for drug development, recommendations
regarding practices and clinical trials, and a research
agenda to advance the science of OA-related biomarkers.
CONCLUSIONS: Although many OA-related biomarkers are
currently available they exist in various states of
qualification and validation. The biomarkers that are likely
to have the earliest beneficial impact on clinical trials
fall into two general categories, those that will allow
targeting of subjects most likely to either respond and/or
progress (prognostic value) within a reasonable and
manageable time frame for a clinical study (for instance
within 1-2 years for an OA trial), and those that provide
early feedback for preclinical decision-making and for trial
organizers that a drug is having the desired biochemical
effect. As in vitro biomarkers are increasingly investigated
in the context of specific drug treatments, advances in the
field can be expected that will lead to rapid expansion of
the list of available biomarkers with increasing
understanding of the molecular processes that they
represent.},
Language = {eng},
Doi = {10.1016/j.joca.2010.08.019},
Key = {fds188644}
}
@article{fds188662,
Author = {VB Kraus},
Title = {Osteoarthritis year 2010 in review: biochemical
markers.},
Journal = {Osteoarthritis and cartilage / OARS, Osteoarthritis Research
Society},
Volume = {19},
Number = {4},
Pages = {346-53},
Year = {2011},
Month = {April},
ISSN = {1522-9653},
url = {http://dx.doi.org/10.1016/j.joca.2011.02.002},
Keywords = {Biological Markers • Biomedical Research • Humans
• Osteoarthritis • metabolism •
metabolism*},
Abstract = {At the 2010 Osteoarthritis Research Society International
(OARSI) congress in Brussels I was asked to present on
"Biochemical Markers" in the "Year in Review" session. This
provided an opportunity to summarize ongoing work and
consensus building in the osteoarthritis research community
related to osteoarthritis biomarkers, and second, and an
opportunity to briefly overview a subset of studies from the
previous 12 months related to soluble biomarkers that
provided novel insights in the field. This review therefore
briefly summarizes the progress in 2010 of the OARSI OA
Biomarkers Global Initiative and the OARSI FDA Biomarkers
Working Group, and provides a summary of selected
osteoarthritis biomarker studies reported over the previous
12 months based on a review of articles from seven
musculoskeletal journals and a PubMed search using the terms
biomarkers and osteoarthritis.},
Language = {eng},
Doi = {10.1016/j.joca.2011.02.002},
Key = {fds188662}
}
@article{fds188635,
Author = {H Lum and R Sloane and KM Huffman and VB Kraus and DK Thompson and WE
Kraus, JR Bain and R Stevens and CF Pieper and GA Taylor and CB Newgard and HJ Cohen and MC Morey},
Title = {Plasma Acylcarnitines Are Associated With Physical
Performance in Elderly Men.},
Journal = {The journals of gerontology. Series A, Biological sciences
and medical sciences},
Year = {2011},
Month = {March},
ISSN = {1758-535X},
url = {http://dx.doi.org/10.1093/gerona/glr006},
Abstract = {BACKGROUND: Metabolic profiling might provide insight into
the biologic underpinnings of disability in older adults.
METHODS: A targeted mass spectrometry-based platform was
used to identify and quantify 45 plasma acylcarnitines in 77
older men with a mean age of 79 years and average body mass
index of 28.4 kg/m(2). To control for type I error inherent
in a test of multiple analytes, principal components
analysis was employed to reduce the acylcarnitines from 45
separate metabolites, into a single "acylcarnitine factor."
We then tested for an association between this acylcarnitine
factor and multiple indices of physical performance and
self-reported function. RESULTS: The acylcarnitine factor
accounted for 40% of the total variance in 45
acylcarnitines. Of the metabolites analyzed, those that
contributed most to our one-factor solution were
even-numbered medium and long-chain species with side chains
containing 10-18 carbons (factor loadings ≥0.70).
Odd-numbered chain species, in contrast, had factor loadings
0.50 or less. Acylcarnitine factor scores were inversely
related to physical performance as measured by the Short
Physical Performance Battery total score, two of its three
component scores (gait and chair stands Short Physical
Performance Battery), and usual and maximal gait speeds (ρ
= -0.324, -0.348, -0.309, -0.241, and -0.254, respectively;
p < .05). CONCLUSIONS: Higher acylcarnitine factor scores
were associated with lower levels of objectively measured
physical performance in this group of older, largely
overweight men. Metabolic profiles of rodents exhibiting
lipid-induced mitochondrial dysfunction show a similar
phenotypic predominance of medium- and long-chain
acylcarnitines.},
Language = {ENG},
Doi = {10.1093/gerona/glr006},
Key = {fds188635}
}
@article{fds188617,
Author = {KD Allen and JM Jordan and M Doherty and JB Renner and VB
Kraus},
Title = {Performance of global assessments of hip, knee, and back
symptom change.},
Journal = {Clinical rheumatology},
Volume = {30},
Number = {3},
Pages = {331-8},
Year = {2011},
Month = {March},
ISSN = {1434-9949},
url = {http://dx.doi.org/10.1007/s10067-010-1536-x},
Abstract = {The objective of this study is to compare patients' global
assessments of change in knee, hip, and back symptoms with
actual changes over time in pain, function, and radiographic
severity. The participants (n = 894, 80% female, mean
age = 66 years) completed two assessments (mean of
4 years apart) as part of a study on the genetics of
generalized osteoarthritis. At both assessments,
participants completed the Western Ontario and McMaster
Universities OA Index (WOMAC), and radiographic severity was
assessed for knees, hips, and low back. At the second
assessment, participants described changes in knee, hip, and
low back symptoms as worse, better, same, or never had
symptoms. Analysis of covariance models examined mean
changes in WOMAC scores and radiographic severity according
to categories of the global assessment measures. Statistical
significance was examined for linear trend. Mean WOMAC
total, pain, and function scores decreased (indicating
improvement) among participants who indicated joint symptoms
were better, showed little change among those who reported
symptoms were the same/never had symptoms, and increased
among those who reported symptoms were worse. For all
analyses except the comparison of WOMAC pain change
according to global assessment of low back symptom change,
there was a statistically significant linear trend
(p < 0.05). Patterns were similar for changes in
radiographic severity, but the tests of linear trend were
not statistically significant. Results support the
concordance of these global assessments of joint symptom
change with actual changes in self-reported symptoms. These
global assessments may be useful for assessing change over
time when baseline data are unavailable.},
Language = {eng},
Doi = {10.1007/s10067-010-1536-x},
Key = {fds188617}
}
@article{fds188634,
Author = {G McDaniel and JB Renner and R Sloane and VB Kraus},
Title = {Association of knee and ankle osteoarthritis with physical
performance.},
Journal = {Osteoarthritis and cartilage / OARS, Osteoarthritis Research
Society},
Year = {2011},
Month = {February},
ISSN = {1522-9653},
url = {http://dx.doi.org/10.1016/j.joca.2011.01.016},
Abstract = {OBJECTIVE: The direct measurement of the ability to perform
physical tasks yields information about factors contributing
to poor function and insights into strategies for preventing
disability. Our goal was to evaluate the relationship of
walking speed and balance tests with specific radiographic
features of knee and ankle osteoarthritis (OA). METHODS: A
timed eight foot walk and a standing balance test were
performed by 138 participants of a longitudinal
observational study of knee OA progression. Radiographic
features of OA severity, joint space narrowing (JSN), a
surrogate for cartilage loss and osteophyte (OST) formation,
were assessed for the knee and ankle. The association of
these performance measures with radiographic OA was
evaluated using correlation analysis, adjusted for age,
gender, body mass index (BMI), and number of comorbidities.
RESULTS: Knee and ankle JSN, but not OST, was negatively
associated with specific performance tests: walking speed
was associated with knee JSN (Spearman rho = -0.20,
P = 0.02) and balance was associated with ankle (subtalar
joint) JSN (Spearman rho = -0.22, P = 0.01). These
relationships remained significant upon further control for
knee and ankle pain. CONCLUSIONS: Structural joint damage
due to OA (JSN in contrast to OST) negatively impacted
specific domains of physical performance. These results
indicate that targeting specific joints for specific
functional outcomes may be indicated, and suggest that
prevention of cartilage damage in these joints is a sensible
target for OA disease modification to prevent
disability.},
Language = {ENG},
Doi = {10.1016/j.joca.2011.01.016},
Key = {fds188634}
}
@article{fds188649,
Author = {LM Redman and KM Huffman and LR Landerman and CF Pieper, JR Bain and MJ
Muehlbauer, RD Stevens and BR Wenner and VB Kraus and CB Newgard and WE
Kraus, E Ravussin},
Title = {Effect of caloric restriction with and without exercise on
metabolic intermediates in nonobese men and
women.},
Journal = {The Journal of clinical endocrinology and
metabolism},
Volume = {96},
Number = {2},
Pages = {E312-21},
Year = {2011},
Month = {February},
ISSN = {1945-7197},
url = {http://dx.doi.org/10.1210/jc.2010-1971},
Keywords = {Adiposity • Adult • Aging • Amino Acids
• Body Composition • Caloric Restriction* •
Carnitine • Cross-Sectional Studies • Data
Interpretation, Statistical • Exercise • Fatty
Acids • Female • Humans • Insulin Resistance
• Male • Metabolism • Middle Aged •
Overweight • Principal Component Analysis • Sex
Characteristics • Spectrum Analysis • Weight Loss
• analogs & derivatives • blood • metabolism
• physiology • physiology*},
Abstract = {OBJECTIVE: The objective of the study was to evaluate
whether serum concentrations of metabolic intermediates are
related to adiposity and insulin sensitivity (Si) in
overweight healthy subjects and compare changes in metabolic
intermediates with similar weight loss achieved by diet only
or diet plus exercise. METHODS: This was a randomized
controlled trial. METHODS: The cross-sectional study
included 46 (aged 36.8 ± 1.0 yr) overweight (body mass
index 27.8 ± 0.7 kg/m(2)) subjects enrolled in a 6-month
study of calorie restriction. To determine the effect of
diet only or diet plus exercise on metabolic intermediates,
35 subjects were randomized to control (energy intake at
100% of energy requirements); CR (25% calorie restriction),
or CR+EX: (12.5% CR plus 12.5% increase in energy
expenditure by exercise). METHODS: Serum concentrations of
eight fatty acids, 15 amino acids, and 45 acylcarnitines
(ACs) measured by targeted mass spectrometry. RESULTS: In
overweight subjects, the concentrations of C2 AC and
long-chain ACs were positively associated with percent fat
(R(2) = 0.75, P = 0.0001) and Si (R(2) = 0.12, P = 0.05).
The percent fat (R(2) = 0.77, P < 0.0001), abdominal
visceral fat (R(2) = 0.64, P < 0.0001), and intrahepatic fat
(R(2) = 0.30, P = 0.0002) were positively associated with
fatty acid concentrations. There was a significant increase
in an AC factor (comprised of C2 and several medium chain
ACs) in the CR group (P = 0.01). CONCLUSIONS: In nonobese
subjects, fasted serum ACs are associated with Si and fat
mass. Despite similar weight loss, serum ACs increase with
CR alone but not CR+EX. A greater improvement in Si with
weight loss during CR+EX interventions may be related to
improved coupling of β-oxidation and tricarboxylic acid
cycle flux induced by exercise.},
Language = {eng},
Doi = {10.1210/jc.2010-1971},
Key = {fds188649}
}
@article{fds188655,
Author = {AE Denoble and KM Huffman and TV Stabler and SJ Kelly and MS Hershfield and GE McDaniel and RE Coleman and VB Kraus},
Title = {Uric acid is a danger signal of increasing risk for
osteoarthritis through inflammasome activation.},
Journal = {Proceedings of the National Academy of Sciences of the
United States of America},
Volume = {108},
Number = {5},
Pages = {2088-93},
Year = {2011},
Month = {February},
ISSN = {1091-6490},
url = {http://dx.doi.org/10.1073/pnas.1012743108},
Keywords = {Aged • Carrier Proteins • Cohort Studies •
Female • Humans • Interleukin-1 •
Interleukin-18 • Knee • Male • Middle Aged
• Osteoarthritis • Risk Factors • Severity of
Illness Index • Uric Acid • biosynthesis •
blood • blood* • genetics • immunology •
pathology*},
Abstract = {Uric acid (UA) is known to activate the NLRP3 (Nacht,
leucine-rich repeat and pyrin domain containing protein 3)
inflammasome. When activated, the NLRP3 (also known as
NALP3) inflammasome leads to the production of IL-18 and
IL-1β. In this cohort of subjects with knee osteoarthritis
(OA), synovial fluid uric acid was strongly correlated with
synovial fluid IL-18 and IL-1β. Synovial fluid uric acid
and IL-18 were strongly and positively associated with OA
severity as measured by both radiograph and bone
scintigraphy, and synovial fluid IL-1β was associated with
OA severity but only by radiograph. Furthermore, synovial
fluid IL-18 was associated with a 3-y change in OA severity,
on the basis of the radiograph. We conclude that synovial
fluid uric acid is a marker of knee OA severity. The
correlation of synovial fluid uric acid with the two
cytokines (IL-18 and IL-1β) known to be produced by uric
acid-activated inflammasomes and the association of synovial
fluid IL-18 with OA progression, lend strong support to the
potential involvement of the innate immune system in OA
pathology and OA progression.},
Language = {eng},
Doi = {10.1073/pnas.1012743108},
Key = {fds188655}
}
@article{fds188616,
Author = {KM Huffman and CA Slentz and LA Bateman and D Thompson and MJ
Muehlbauer, JR Bain and RD Stevens and BR Wenner and VB Kraus and CB
Newgard, WE Kraus},
Title = {Exercise-induced changes in metabolic intermediates,
hormones, and inflammatory markers associated with
improvements in insulin sensitivity.},
Journal = {Diabetes care},
Volume = {34},
Number = {1},
Pages = {174-6},
Year = {2011},
Month = {January},
ISSN = {1935-5548},
url = {http://dx.doi.org/10.2337/dc10-0709},
Abstract = {OBJECTIVE: To understand relationships between exercise
training-mediated improvements in insulin sensitivity (S(I))
and changes in circulating concentrations of metabolic
intermediates, hormones, and inflammatory mediators.
METHODS: Targeted mass spectrometry and enzyme-linked
immunosorbent assays were used to quantify metabolic
intermediates, hormones, and inflammatory markers at
baseline, after 6 months of exercise training, and 2 weeks
after exercise training cessation (n = 53). A principal
components analysis (PCA) strategy was used to relate
changes in these intermediates to changes in S(I). RESULTS:
PCA reduced the number of intermediates from 90 to 24
factors composed of biologically related components. With
exercise training, improvements in S(I) were associated with
reductions in by-products of fatty acid oxidation and
increases in glycine and proline (P < 0.05, R² = 0.59);
these relationships were retained 15 days after cessation of
exercise training (P < 0.05, R² = 0.34). CONCLUSIONS: These
observations support prior observations in animal models
that exercise training promotes more efficient mitochondrial
β-oxidation and challenges current hypotheses regarding
exercise training and glycine metabolism.},
Language = {eng},
Doi = {10.2337/dc10-0709},
Key = {fds188616}
}
@article{fds188631,
Author = {AW Cheng and TV Stabler and M Bolognesi and VB Kraus},
Title = {Selenomethionine inhibits IL-1β inducible nitric oxide
synthase (iNOS) and cyclooxygenase 2 (COX2) expression in
primary human chondrocytes.},
Journal = {Osteoarthritis and cartilage / OARS, Osteoarthritis Research
Society},
Volume = {19},
Number = {1},
Pages = {118-25},
Year = {2011},
Month = {January},
ISSN = {1522-9653},
url = {http://dx.doi.org/10.1016/j.joca.2010.10.019},
Keywords = {Aged • Blotting, Western • Cells, Cultured •
Chondrocytes • Cyclooxygenase 2 • Dinoprostone
• Humans • Interleukin-1beta • Middle Aged
• Nitric Oxide Synthase • RNA, Messenger •
Selenomethionine • antagonists & inhibitors* •
drug effects • drug effects* • metabolism •
metabolism* • pharmacology*},
Abstract = {OBJECTIVE: Several lines of evidence show that selenium (Se)
has potential protective effects in osteoarthritis (OA),
however the exact mechanism is still unclear. As
interleukin-1β (IL-1β) is one of the key proinflammatory
cytokines contributing to the progression in OA, we
investigated the effect of Se in neutralizing the
inflammatory effects of IL-1β on nitric oxide (NO) and
prostaglandin E₂ (PGE₂) production, and the signaling
pathways involved. METHODS: Isolated primary human
chondrocytes were pretreated with selenomethionine (SeMet)
(0.5 μM SeMet) for 24 h then co-treated without or with
IL-1β (10 pg/ml or 50 pg/ml) for another 24 h followed by
RNA isolation. Gene expression of inducible nitric oxide
synthase (iNOS) and cyclooxygenase-2 (COX2) was determined
by quantitative Real Time-Polymerase Chain Reaction. Culture
media concentrations of NO and PGE₂ were determined by
nitrite (NO₂⁻) assay and immunoassay respectively. For
analysis of cell signaling pathways, chondrocytes were
pretreated with SeMet then stimulated with IL-1β for 0-45
min. The activity of IL-1β signaling pathways was
determined by Western blot screening of phosphorylation
states of signal transduction proteins. RESULTS: SeMet
inhibited chondrocyte gene expression of IL-1β induced iNOS
(31-54%, P=0.031) and COX2 (50-65%, P=0.031) with
corresponding reductions in both NO (19-47%, P=0.031) and
PGE₂ (24-32%, P=0.031) production. Pretreatment with SeMet
attenuated IL-1β induced activation of p38 MAPK (39%,
P=0.039) but not the extracellular signal-regulated kinase
pathways (ERK) 1/2, c-Jun N-terminal kinases (JNK) or
nuclear factor κB (NFκB). CONCLUSIONS: This study
elucidates one potential protective mechanism of Se, namely
through the alteration of cell signaling and downstream
transcription of pro-inflammatory effects of
IL-1β.},
Language = {eng},
Doi = {10.1016/j.joca.2010.10.019},
Key = {fds188631}
}
@article{fds188615,
Title = {Schmitz N, Laverty S, Kraus VB, Aigner T. Response to Letter
to the Editor: 'India ink and cartilage'. Osteoarthritis
Cartilage. 2011 Mar;19(3):333-5.},
Year = {2011},
Key = {fds188615}
}
@article{fds188613,
Author = {VB Kraus and JL Huebner and J DeGroot and A Bendele},
Title = {The OARSI histopathology initiative - recommendations for
histological assessments of osteoarthritis in the guinea
pig.},
Journal = {Osteoarthritis and cartilage / OARS, Osteoarthritis Research
Society},
Volume = {18 Suppl 3},
Pages = {S35-52},
Year = {2010},
Month = {October},
ISSN = {1522-9653},
url = {http://dx.doi.org/10.1016/j.joca.2010.04.015},
Keywords = {Animals • Arthritis, Experimental • Disease
Models, Animal • Guinea Pigs • Histocytological
Preparation Techniques • Joints • Osteoarthritis
• Severity of Illness Index • Synovial Membrane
• Synovitis • methods • pathology •
pathology*},
Abstract = {OBJECTIVE: This review focuses on the criteria for assessing
osteoarthritis (OA) in the guinea pig at the macroscopic and
microscopic levels, and recommends particular assessment
criteria to assist standardization in the conduct and
reporting of preclinical trails in guinea pig models of OA.
METHODS: A review was conducted of all OA studies from 1958
until the present that utilized the guinea pig. The PubMed
database was originally searched August 1, 2006 using the
following search terms: guinea pig and OA. We continued to
check the database periodically throughout the process of
preparing this chapter and the final search was conducted
January 7, 2009. Additional studies were found in a review
of abstracts from the OsteoArthritis Research Society
International (OARSI) conferences, Orthopaedic Research
Society (ORS) conferences, and literature related to
histology in other preclinical models of OA reviewed for
relevant references. Studies that described or used systems
for guinea pig joint scoring on a macroscopic, microscopic,
or ultrastructural basis were included in the final
comprehensive summary and review. General recommendations
regarding methods of OA assessment in the guinea pig were
derived on the basis of a comparison across studies and an
inter-rater reliability assessment of the recommended
scoring system. RESULTS: A histochemical-histological
scoring system (based on one first introduced by H. Mankin)
is recommended for semi-quantitative histological assessment
of OA in the guinea pig, due to its already widespread
adoption, ease of use, similarity to scoring systems used
for OA in humans, its achievable high inter-rater
reliability, and its demonstrated correlation with synovial
fluid biomarker concentrations. Specific recommendations are
also provided for histological scoring of synovitis and
scoring of macroscopic lesions of OA. CONCLUSIONS: As
summarized herein, a wealth of tools exist to aid both in
the semi-quantitative and quantitative assessment of OA in
the guinea pig and provide a means of comprehensively
characterizing the whole joint organ. In an ongoing effort
at standardization, we recommend specific criteria for
assessing the guinea pig model of OA as part of an OARSI
initiative, termed herein the OARSI-HISTOgp
recommendations.},
Language = {eng},
Doi = {10.1016/j.joca.2010.04.015},
Key = {fds188613}
}
@article{fds188621,
Author = {N Schmitz and S Laverty and VB Kraus and T Aigner},
Title = {Basic methods in histopathology of joint
tissues.},
Journal = {Osteoarthritis and cartilage / OARS, Osteoarthritis Research
Society},
Volume = {18 Suppl 3},
Pages = {S113-6},
Year = {2010},
Month = {October},
ISSN = {1522-9653},
url = {http://dx.doi.org/10.1016/j.joca.2010.05.026},
Keywords = {Animals • Arthritis, Experimental • Collagen
• Disease Models, Animal • Histocytological
Preparation Techniques • Humans • Osteoarthritis
• Proteoglycans • Staining and Labeling •
metabolism • methods • pathology*},
Abstract = {Histological and histochemical methods are important tools
in the evaluation of joint tissue samples for degenerative
joint diseases, both in humans and in animal models. In this
respect, standardized, simple, and reliable techniques are
mandatory. This chapter describes five basic staining
procedures appropriate for macroscopic (Indian ink) and
histologic (HE/hematoxylin - eosin) visualization and
scoring of cartilage proteoglycan and collagen content
(toluidine blue/safranin O and picrosirius red/Goldner's
trichrome).},
Language = {eng},
Doi = {10.1016/j.joca.2010.05.026},
Key = {fds188621}
}
@article{fds188623,
Author = {T Aigner and JL Cook and N Gerwin and SS Glasson and S Laverty and CB
Little, W McIlwraith and VB Kraus},
Title = {Histopathology atlas of animal model systems - overview of
guiding principles.},
Journal = {Osteoarthritis and cartilage / OARS, Osteoarthritis Research
Society},
Volume = {18 Suppl 3},
Pages = {S2-6},
Year = {2010},
Month = {October},
ISSN = {1522-9653},
url = {http://dx.doi.org/10.1016/j.joca.2010.07.013},
Keywords = {Animals • Arthritis, Experimental • Atlases as
Topic* • Consensus Development Conferences as Topic
• Disease Models, Animal* • Osteoarthritis •
Severity of Illness Index* • Species Specificity •
Terminology as Topic • pathology*},
Abstract = {Animal model systems represent an important adjunct and
surrogate for studies of osteoarthritis (OA) in humans. They
provide a means to study OA pathophysiology as well as aid
in the development of therapeutic agents and biological
markers for diagnosing and prognosing the disease. Thus, it
is of great importance for the OA scientific community, both
in academic as well as industrial research, to standardize
scoring systems for evaluating the OA disease process and to
make results between different studies comparable. The task
of the histopathology initiative of OARSI was to achieve a
consensus of scoring systems for the most important species
used in OA animal model research (dog, guinea pig, horse,
mouse, rabbit, rat, and sheep/goat), which are presented in
the various chapters in this special volume of
Osteoarthritis & Cartilage together with extra chapters on
basic methodology (histochemistry, statistics, morphometry),
the specific terminology and a general discussion of animal
models in OA research. Standardized definitions are
suggested for basic but essential terms such as "grading"
and "staging" in order to promote their consistent use and
thereby promote improved understanding and data
interpretation across all model systems. Thus, this
introductory chapter presents an overview of the guiding
principles for assessment of important OA animal model
systems. Use of such systems, independently or in
conjunction with other systems in parallel, should
facilitate comparability of results across animal model
studies.},
Language = {eng},
Doi = {10.1016/j.joca.2010.07.013},
Key = {fds188623}
}
@article{fds188629,
Author = {B Chuckpaiwong and HC Charles and VB Kraus and F Guilak and JA
Nunley},
Title = {Age-associated increases in the size of the infrapatellar
fat pad in knee osteoarthritis as measured by 3T
MRI.},
Journal = {Journal of orthopaedic research : official publication of
the Orthopaedic Research Society},
Volume = {28},
Number = {9},
Pages = {1149-54},
Year = {2010},
Month = {September},
ISSN = {1554-527X},
url = {http://dx.doi.org/10.1002/jor.21125},
Keywords = {Adipokines • Adipose Tissue • Aged • Aging
• Body Mass Index • Cohort Studies • Humans
• Imaging, Three-Dimensional • Knee Joint •
Magnetic Resonance Imaging • Middle Aged • Obesity
• Osteoarthritis, Knee • Pain • Patella
• Reproducibility of Results • Risk Factors •
Weight-Bearing • epidemiology • metabolism •
methods* • pathology • pathology* •
physiology • physiopathology •
standards},
Abstract = {Obesity, as a primary risk factor for osteoarthritis (OA),
has been shown to alter joint loading, but may also result
in metabolic changes characterized by chronic, low-level
inflammation due to increased circulating levels of
adipose-derived cytokines, or "adipokines." The presence of
the infrapatellar fat pad in the knee suggests that local
changes in adipokine concentrations may influence knee OA.
This study examined the hypotheses that the volume of the
infrapatellar fat pad is correlated to the body mass index
(BMI) of OA patients, and that fat pad volume is greater in
subjects with OA. Fat pad volume was measured in sequential
magnetic resonance (MR) images taken over one year in a
cohort of 15 control and 15 knee OA subjects. No differences
were observed in the fat pad volume between the two groups
at baseline, 3, 6, or 12 months. In control subjects, no
significant correlations were present between any parameters
(age, BMI, weight, volume of fat pad at any time point).
However, in the osteoarthritic group, fat pad volume was
correlated with age at every time point. One possible
explanation is that local factors related to knee OA may
also induce enlargement of the fat pad with age.
Alternatively, subjects who are prone to growth or
enlargement of the fat pad may also be more prone to
symptomatic OA. These findings provide intriguing
preliminary data on the potential role of the infrapatellar
fat pad in OA, although additional study is required to
better understand the mechanisms of this
relationship.},
Language = {eng},
Doi = {10.1002/jor.21125},
Key = {fds188629}
}
@article{fds188632,
Author = {F Kempta Lekpa and JC Piette and S Bastuji-Garin and VB Kraus and TV
Stabler, AR Poole and A Marini-Portugal and X Chevalier},
Title = {Serum cartilage oligomeric matrix protein (COMP) level is a
marker of disease activity in relapsing polychondritis.},
Journal = {Clinical and experimental rheumatology},
Volume = {28},
Number = {4},
Pages = {553-5},
Year = {2010},
Month = {August},
ISSN = {0392-856X},
Keywords = {Adult • Biological Markers • Chondroitin Sulfates
• Extracellular Matrix Proteins • Female •
Glycoproteins • Humans • Male • Matrix
Metalloproteinase 8 • Middle Aged •
Polychondritis, Relapsing • Prognosis •
Retrospective Studies • Severity of Illness Index*
• Steroids • blood • blood* • diagnosis
• drug therapy • therapeutic use},
Abstract = {OBJECTIVE: Relapsing polychondritis (RP) is a rare and
severe disease which may lead to destruction of elastic
cartilages. Until now, no reliable biomarker of disease
activity in RP has been available. This study was designed
to measure serum levels of cartilage biomarkers during both
active and inactive phases of the disease. METHODS: Serum
levels of cartilage oligomeric matrix protein (COMP),
chondroitin sulfate 846 epitope (CS846) of proteoglycan
aggrecan and collagen type II collagenase cleavage
neoepitope (C2C) were measured retrospectively in 21
subjects with RP. The Wilcoxon matched-pairs signed-rank
test was used for statistical comparisons of biomarker
levels in active and inactive phases of RP. RESULTS: Only
the serum level of COMP was significantly increased during
disease flares. Steroids did not alter the serum
cartilage-related biomarker levels. However, during the
active phase, C2C levels were significantly higher in
steroid treated patients compared with non-steroid treated
patients. CONCLUSIONS: This study suggests that serum COMP
level may be useful for monitoring disease activity of RP.
Further prospective studies are required to confirm this
result.},
Language = {eng},
Key = {fds188632}
}
@article{fds188630,
Author = {VB Kraus and M Nevitt and LJ Sandell},
Title = {Summary of the OA biomarkers workshop 2009--biochemical
biomarkers: biology, validation, and clinical
studies.},
Journal = {Osteoarthritis and cartilage / OARS, Osteoarthritis Research
Society},
Volume = {18},
Number = {6},
Pages = {742-5},
Year = {2010},
Month = {June},
ISSN = {1522-9653},
url = {http://dx.doi.org/10.1016/j.joca.2010.02.014},
Keywords = {Biological Markers • Biomedical Research • Disease
Progression • Humans • Osteoarthritis •
Reproducibility of Results • analysis •
classification* • standards},
Abstract = {Osteoarthritis (OA) biomarkers that can measure and predict
the full spectrum of disease progression and outcomes are
needed, but few, if any, such biomarkers have been validated
for this purpose. The Osteoarthritis Research Society
International (OARSI) has organized an OA Biomarkers Global
Initiative. As a part of this Initiative, three workshops
have been planned to occur over the next 4 years to focus on
identifying and removing obstacles to progress in the field
and planning the way forward. In addition to OARSI, the
National Institute of Arthritis, Musculoskeletal, and Skin
Disease, the Arthritis Foundation, the Orthopaedic Research
Society, and the American Orthopaedic Sports Medicine
Society cosponsored the first meeting April 23-24, 2009.
Organizers brought together thought and research leaders in
the field, young investigators, biomarkers researchers with
insights from other fields, clinical investigators with a
responsibility for OA sample and resource management,
funding agencies, and commercial entities with an interest
in the commercial propagation as well as the application of
markers in OA.},
Language = {eng},
Doi = {10.1016/j.joca.2010.02.014},
Key = {fds188630}
}
@article{fds188639,
Author = {AE Nelson and YM Golightly and VB Kraus and T Stabler and JB Renner and CG
Helmick, JM Jordan},
Title = {Serum transforming growth factor-beta 1 is not a robust
biomarker of incident and progressive radiographic
osteoarthritis at the hip and knee: the Johnston County
Osteoarthritis Project.},
Journal = {Osteoarthritis and cartilage / OARS, Osteoarthritis Research
Society},
Volume = {18},
Number = {6},
Pages = {825-9},
Year = {2010},
Month = {June},
ISSN = {1522-9653},
url = {http://dx.doi.org/10.1016/j.joca.2010.02.013},
Keywords = {African Americans • African Continental Ancestry Group
• Aged • Biological Markers • Disease
Progression • European Continental Ancestry Group
• Female • Humans • Longitudinal Studies
• Male • Middle Aged • Osteoarthritis, Hip
• Osteoarthritis, Knee • Predictive Value of Tests
• Proportional Hazards Models • Transforming
Growth Factor beta1 • blood • blood* •
pathology • radiography},
Abstract = {OBJECTIVE: To test whether serum transforming growth
factor-beta 1 (TGF-beta1) predicts incident and progressive
hip or knee radiographic OA (rOA). METHODS: Serum TGF-beta1
was measured for 330 participants aged 45 years and older in
the Johnston County Osteoarthritis Project, with paired
longitudinal films available for 618 hips and 658 knees.
Incident and progressive rOA were defined using
Kellgren-Lawrence (K-L) grade as well as osteophyte (OST)
and joint space narrowing (JSN) scores. Natural logarithm
transformation was used to produce near-normal distributions
for continuous TGF-beta1 (lnTGF-beta1). Separate
multivariable Weibull regression models were used to provide
hazard ratios (HRs) for a 1-unit increase lnTGF-beta1 with
each rOA outcome, accounting for variable follow-up times
and clustering by individual, adjusted for age, race,
gender, and body mass index (BMI). Interaction terms were
considered statistically significant at P<0.10. RESULTS: The
mean (+/-SD) age of the sample was 61.9+/-9.7 years, the
mean BMI was 30.3+/-6.9 kg/m(2), with 60.6% women and 42.4%
AA. The mean (+/-SD) TGF-beta1 was 17.8+/-6.1 ng/ml;
follow-up time was 6.1+/-1.3 years. There were no
significant interactions by race or gender. HRs showed no
significant relationship between lnTGF-beta1 and incident or
progressive rOA, OST, or JSN, at the knee or the hip.
CONCLUSIONS: Levels of TGF-beta1 do not predict incident or
progressive rOA, OST, or JSN at the hip or knee in this
longitudinal, population-based study, making it unlikely
that TGF-beta1 will be a robust biomarker for rOA in future
studies.},
Language = {eng},
Doi = {10.1016/j.joca.2010.02.013},
Key = {fds188639}
}
@article{fds188620,
Author = {N Schmitz and VB Kraus and T Aigner},
Title = {Targets to tackle--the pathophysiology of the
disease.},
Journal = {Current drug targets},
Volume = {11},
Number = {5},
Pages = {521-7},
Year = {2010},
Month = {May},
ISSN = {1873-5592},
Keywords = {Bone Matrix • Cartilage • Chondrocytes •
Collagen • Drug Delivery Systems • Humans •
Inflammation Mediators • Joint Capsule • Joints
• Models, Biological • Osteoarthritis •
Synovial Membrane • anatomy & histology •
metabolism • methods* • pathology •
physiology* • physiopathology*},
Abstract = {Osteoarthritis, the degeneration of the joints, is the
leading source of physical disability with severely impaired
quality of life due to pain and loss of joint functioning in
industrialized nations. Clinically, degeneration affects
mostly the large weight bearing joints of the legs like the
hip or the knees, but in principle it can affect any joint
of the body. Osteoarthritis represents a disease group with
disease subsets that have different underlying
pathophysiological mechanisms. Therefore primary
osteoarthritis has to be distinguished from secondary forms
of the disease, which are due to traumatic events, endocrine
or metabolic disorders etc. The enormous frequency of this
disease makes osteoarthritis one of the most expensive
conditions in the Western world, both in terms of direct as
well as indirect costs. So far, despite intensive efforts
over several decades, the success of disease-modifying
approaches have been rather limited and mostly restricted to
analgesis and non-pharmacologic therapy (e.g. nonsteroidal
anti-inflammatory agents, exercise, and physiotherapy).
Joint replacement is still the unsurpassed therapy for the
symptomatic relief of advanced and incapacitating OA. It is
evident that there is a great need for the development of
disease modifying agents in order to improve quality of life
as well as to relieve the community of the enormous
socio-economic burden of the disease.},
Language = {eng},
Key = {fds188620}
}
@article{fds188636,
Author = {M Attur and HY Wang and VB Kraus and JF Bukowski and N Aziz and S
Krasnokutsky, J Samuels and J Greenberg and G McDaniel and SB
Abramson, KS Kornman},
Title = {Radiographic severity of knee osteoarthritis is conditional
on interleukin 1 receptor antagonist gene
variations.},
Journal = {Annals of the rheumatic diseases},
Volume = {69},
Number = {5},
Pages = {856-61},
Year = {2010},
Month = {May},
ISSN = {1468-2060},
url = {http://dx.doi.org/10.1136/ard.2009.113043},
Keywords = {Adult • Aged • Aging • Female • Genetic
Markers • Genetic Predisposition to Disease •
Genotype • Haplotypes • Humans • Inflammation
Mediators • Interleukin 1 Receptor Antagonist Protein
• Male • Middle Aged • Osteoarthritis, Knee
• Polymorphism, Single Nucleotide • Severity of
Illness Index • Synovial Fluid • analysis •
chemistry • genetics • genetics* • metabolism
• pathology • radiography},
Abstract = {BACKGROUND: A lack of biomarkers that identify patients at
risk for severe osteoarthritis (OA) complicates development
of disease-modifying OA drugs. OBJECTIVE: To determine
whether inflammatory genetic markers could stratify patients
with knee OA into high and low risk for destructive disease.
METHODS: Genotype associations with knee OA severity were
assessed in two Caucasian populations. Fifteen single
nucleotide polymorphisms (SNPs) in six inflammatory genes
were evaluated for association with radiographic severity
and with synovial fluid mediators in a subset of the
patients. RESULTS: Interleukin 1 receptor antagonist (IL1RN)
SNPs (rs419598, rs315952 and rs9005) predicted
Kellgren-Lawrence scores independently in each population.
One IL1RN haplotype was associated with lower odds of
radiographic severity (OR=0.15; 95% CI 0.065 to 0.349;
p<0.0001), greater joint space width and lower synovial
fluid cytokine levels. Carriage of the IL1RN haplotype
influenced the age relationship with severity. CONCLUSIONS:
IL1RN polymorphisms reproducibly contribute to disease
severity in knee OA and may be useful biomarkers for patient
selection in disease-modifying OA drug trials.},
Language = {eng},
Doi = {10.1136/ard.2009.113043},
Key = {fds188636}
}
@article{fds188648,
Author = {VB Kraus},
Title = {Waiting for action on the osteoarthritis
front.},
Journal = {Current drug targets},
Volume = {11},
Number = {5},
Pages = {518-20},
Year = {2010},
Month = {May},
ISSN = {1873-5592},
Keywords = {Disease Progression* • Humans • Osteoarthritis
• therapy*},
Language = {eng},
Key = {fds188648}
}
@article{fds188618,
Author = {JL Huebner and JM Williams and M Deberg and Y Henrotin and VB
Kraus},
Title = {Collagen fibril disruption occurs early in primary guinea
pig knee osteoarthritis.},
Journal = {Osteoarthritis and cartilage / OARS, Osteoarthritis Research
Society},
Volume = {18},
Number = {3},
Pages = {397-405},
Year = {2010},
Month = {March},
ISSN = {1522-9653},
url = {http://dx.doi.org/10.1016/j.joca.2009.09.011},
Keywords = {Animals • Biological Markers • Cartilage,
Articular • Collagen Type II • Disease Models,
Animal • Fibril-Associated Collagens • Guinea Pigs
• Immunohistochemistry • Knee Joint • Male
• Osteoarthritis, Knee • Time Factors •
metabolism* • pathology • pathology*},
Abstract = {OBJECTIVE: A major barrier inhibiting the discovery of
structural modifying agents for osteoarthritis (OA) is an
incomplete understanding of early disease events. Herein, we
investigated the time course of collagen II cleavage and
fibril disruption in the well-validated Hartley guinea pig
model of spontaneous OA of the knee. METHODS: Knee joints of
46 male Hartley guinea pigs were analyzed at 3 weeks, 2, 4,
7, 10, 12, and 18 months of age for histological severity of
OA, cartilage collagen fibril disruption by
semi-quantitative polarized light microscopy, and expression
of type II collagen degradation biomarkers, 9A4 and Coll2-1,
by immunohistochemistry. In addition, serum biomarkers
specific for collagen II degradation, CTX-II, C2C, and
Coll2-1 were quantified. RESULTS: Collagen fibril disruption
and expression of the collagenase-generated cleavage
neoepitope, 9A4, were observed as early as 2 months of age,
despite the appearance of histological OA at 4 months of
age. Only serum Coll2-1 increased coincident with the early
disruption of the collagen fibril between 3 weeks and 7
months, in contrast to serum C2C, which did not change
significantly or correlate with histological severity.
Inversely, CTX-II declined dramatically from 3 weeks to 4
months and remaining low thereafter, coincident with growth
plate turnover. CONCLUSIONS: Collagenase cleavage and
disruption of the type II collagen network are early OA
disease events in this model, preceding histological
evidence of proteoglycan loss. The markedly different serum
profiles of collagen II-related biomarkers during the early
stages of disease development suggest compartmental
segregation and temporal regulation of collagen degrading
enzymes.},
Language = {eng},
Doi = {10.1016/j.joca.2009.09.011},
Key = {fds188618}
}
@article{fds188653,
Author = {HC Chen and VB Kraus and YJ Li and S Nelson and C Haynes and J Johnson and T
Stabler, ER Hauser and SG Gregory and WE Kraus and SH
Shah},
Title = {Genome-wide linkage analysis of quantitative biomarker
traits of osteoarthritis in a large, multigenerational
extended family.},
Journal = {Arthritis and rheumatism},
Volume = {62},
Number = {3},
Pages = {781-90},
Year = {2010},
Month = {March},
ISSN = {1529-0131},
url = {http://dx.doi.org/10.1002/art.27288},
Keywords = {Biological Markers • Collagen Type II •
Extracellular Matrix Proteins • Genetic Linkage* •
Genetic Loci • Genome-Wide Association Study •
Glycoproteins • Humans • Hyaluronic Acid •
Lod Score • Osteoarthritis • Pedigree •
Polymorphism, Single Nucleotide • analysis •
blood* • genetics*},
Abstract = {OBJECTIVE: The genetic contributions to the multifactorial
disorder osteoarthritis (OA) have been increasingly
recognized. The goal of the current study was to use
OA-related biomarkers of severity and disease burden as
quantitative traits to identify genetic susceptibility loci
for OA. METHODS: In a large multigenerational extended
family (n = 350), we measured 5 OA-related biomarkers:
hyaluronan (HA), cartilage oligomeric matrix protein (COMP),
N-propeptide of type IIA collagen (PIIANP), C-propeptide of
type II procollagen (CPII), and type II collagen neoepitope
(C2C). Single-nucleotide polymorphism markers (n = 6,090)
covering the whole genome were genotyped using the Illumina
HumanLinkage-12 BeadChip. Variance components analysis, as
implemented in the Sequential Oligogenic Linkage Analysis
Routines, was used to estimate heritabilities of the
quantitative traits and to calculate 2-point and multipoint
logarithm of odds (LOD) scores using a polygenic model.
RESULTS: After adjusting for age and sex, we found that 4 of
the 5 biomarkers exhibited significant heritability (PIIANP
0.57, HA 0.49, COMP 0.43, C2C 0.30; P < or = 0.01 for all).
Fourteen of the 19 loci that had multipoint LOD scores of
>1.5 were near to or overlapped with previously reported OA
susceptibility loci. Four of these loci were identified by
more than 1 biomarker. The maximum multipoint LOD scores for
the heritable quantitative biomarker traits were 4.3 for
PIIANP (chromosome 8p23.2), 3.2 for COMP (chromosome
8q11.1), 2.0 for HA (chromosome 6q16.3), and 2.0 for C2C
(chromosome 5q31.2). CONCLUSIONS: Herein, we report the
first evidence of genetic susceptibility loci identified by
OA-related biomarkers in an extended family. Our results
demonstrate that serum concentrations of PIIANP, HA, COMP,
and C2C have substantial heritable components, and using
these biomarkers, several genetic loci potentially
contributing to the genetic diversity of OA were
identified.},
Language = {eng},
Doi = {10.1002/art.27288},
Key = {fds188653}
}
@article{fds188650,
Author = {G McDaniel and KL Mitchell and C Charles and VB Kraus},
Title = {A comparison of five approaches to measurement of anatomic
knee alignment from radiographs.},
Journal = {Osteoarthritis and cartilage / OARS, Osteoarthritis Research
Society},
Volume = {18},
Number = {2},
Pages = {273-7},
Year = {2010},
Month = {February},
ISSN = {1522-9653},
url = {http://dx.doi.org/10.1016/j.joca.2009.10.005},
Keywords = {Adult • Aged • Bone Malalignment • Female
• Femur • Humans • Male • Middle Aged
• Observer Variation • Osteoarthritis, Knee •
Reproducibility of Results • Tibia • diagnosis*
• radiography*},
Abstract = {OBJECTIVE: The recent recognition of the correlation of the
hip-knee-ankle angle (HKA) with femur-tibia angle (FTA) on a
standard knee radiograph has led to the increasing inclusion
of FTA assessments in OA studies due to its clinical
relevance, cost effectiveness and minimal radiation
exposure. Our goal was to investigate the performance
metrics of currently used methods of FTA measurement to
determine whether a specific protocol could be recommended
based on these results. METHODS: Inter- and intra-rater
reliability of FTA measurements were determined by
intraclass correlation coefficient (ICC) of two independent
analysts. Minimal detectable differences were determined and
the correlation of FTA and HKA was analyzed by linear
regression. Differences among methods of measuring HKA were
assessed by ANOVA. RESULTS: All five methods of FTA
measurement demonstrated high precision by inter- and
intra-rater reproducibility (ICCs>or=0.93). All five methods
displayed good accuracy, but after correction for the offset
of FTA from HKA, the femoral notch landmark method was the
least accurate. However, the methods differed according to
their minimal detectable differences; the FTA methods
utilizing the center of the base of the tibial spines or the
center of the tibial plateau as knee center landmarks
yielded the smallest minimal detectable differences (1.25
degrees and 1.72 degrees, respectively). CONCLUSIONS: All
methods of FTA were highly reproducible, but varied in their
accuracy and sensitivity to detect meaningful differences.
Based on these parameters we recommend standardizing
measurement angles with vertices at the base of the tibial
spines or the center of the tibia and comparing single-point
and two-point methods in larger studies.},
Language = {eng},
Doi = {10.1016/j.joca.2009.10.005},
Key = {fds188650}
}
@article{fds188652,
Author = {MP Le Graverand and RJ Buck and BT Wyman and E Vignon and SA Mazzuca and KD
Brandt, M Piperno and HC Charles and M Hudelmaier and DJ Hunter and C
Jackson, VB Kraus and TM Link and S Majumdar and PV Prasad and TJ
Schnitzer, A Vaz and W Wirth and F Eckstein},
Title = {Change in regional cartilage morphology and joint space
width in osteoarthritis participants versus healthy
controls: a multicentre study using 3.0 Tesla MRI and
Lyon-Schuss radiography.},
Journal = {Annals of the rheumatic diseases},
Volume = {69},
Number = {1},
Pages = {155-62},
Year = {2010},
Month = {January},
ISSN = {1468-2060},
url = {http://dx.doi.org/10.1136/ard.2008.099762},
Keywords = {Adult • Aged • Cartilage, Articular • Disease
Progression • Female • Follow-Up Studies •
Humans • Knee Joint • Magnetic Resonance Imaging
• Middle Aged • Osteoarthritis, Knee •
Severity of Illness Index • methods • pathology*
• radiography},
Abstract = {OBJECTIVE: Cartilage morphology displays sensitivity to
change in osteoarthritis (OA) with quantitative MRI (qMRI).
However, (sub)regional cartilage thickness change at 3.0
Tesla (T) has not been directly compared with radiographic
progression of joint space narrowing in OA participants and
non-arthritic controls. METHODS: A total of 145 women were
imaged at 7 clinical centres: 86 were non-obese and
asymptomatic without radiographic OA and 55 were obese with
symptomatic and radiographic OA (27 Kellgren-Lawrence grade
(KLG)2 and 28 KLG3). Lyon-Schuss (LS) and fixed flexion (FF)
radiographs were obtained at baseline, 12 and 24 months, and
coronal spoiled gradient echo MRI sequences at 3.0 T at
baseline, 6, 12 and 24 months. (Sub)regional, femorotibial
cartilage thickness and minimum joint space width (mJSW) in
the medial femorotibial compartment were measured and the
standardised response means (SRMs) determined. RESULTS: At 6
months, qMRI demonstrated a -3.7% "annualised" change in
cartilage thickness (SRM -0.33) in the central medial
femorotibial compartment (cMFTC) of KLG3 subjects, but no
change in KLG2 subjects. The SRM for mJSW in 12-month LS/FF
radiographs of KLG3 participants was -0.68/-0.13 and at 24
months was -0.62/-0.20. The SRM for cMFTC changes measured
with qMRI was -0.32 (12 months; -2.0%) and -0.48 (24 months;
-2.2%), respectively. CONCLUSIONS: qMRI and LS radiography
detected significant change in KLG3 participants at high
risk of progression, but not in KLG2 participants, and only
small changes in controls. At 12 and 24 months, LS displayed
greater, and FF less, sensitivity to change in KLG3
participants than qMRI.},
Language = {eng},
Doi = {10.1136/ard.2008.099762},
Key = {fds188652}
}
@article{fds188628,
Title = {Lotz MK, Kraus VB. Correction: Posttraumatic osteoarthritis:
pathogenesis and pharmacological treatment options.
Arthritis Res Ther. 2010;12(6):408.},
Year = {2010},
Key = {fds188628}
}
@article{fds188625,
Author = {TM Griffin and B Fermor and JL Huebner and VB Kraus and RM Rodriguiz and WC
Wetsel, L Cao and LA Setton and F Guilak},
Title = {Diet-induced obesity differentially regulates behavioral,
biomechanical, and molecular risk factors for osteoarthritis
in mice.},
Journal = {Arthritis research & therapy},
Volume = {12},
Number = {4},
Pages = {R130},
Year = {2010},
ISSN = {1478-6362},
url = {http://dx.doi.org/10.1186/ar3068},
Keywords = {Adipokines • Animals • Behavior, Animal •
Cartilage • Dietary Fats • Disease Progression
• Extracellular Matrix • Female •
Interleukin-1 • Mice • Mice, Inbred C57BL •
Motor Activity • Obesity • Osteoarthritis, Knee
• Pain • Risk Factors • Severity of Illness
Index • Swine • Temporomandibular Joint Disorders
• Tissue Culture Techniques • blood •
epidemiology • epidemiology* • metabolism •
metabolism* • pharmacology* • physiology •
physiopathology},
Abstract = {INTRODUCTION : Obesity is a major risk factor for the
development of osteoarthritis in both weight-bearing and
nonweight-bearing joints. The mechanisms by which obesity
influences the structural or symptomatic features of
osteoarthritis are not well understood, but may include
systemic inflammation associated with increased adiposity.
In this study, we examined biomechanical, neurobehavioral,
inflammatory, and osteoarthritic changes in C57BL/6J mice
fed a high-fat diet. METHODS : Female C57BL/6J mice were fed
either a 10% kcal fat or a 45% kcal fat diet from 9 to 54
weeks of age. Longitudinal changes in musculoskeletal
function and inflammation were compared with endpoint
neurobehavioral and osteoarthritic disease states. Bivariate
and multivariate analyses were conducted to determine
independent associations with diet, percentage body fat, and
knee osteoarthritis severity. We also examined healthy
porcine cartilage explants treated with physiologic doses of
leptin, alone or in combination with IL-1α and palmitic and
oleic fatty acids, to determine the effects of leptin on
cartilage extracellular matrix homeostasis. RESULTS : High
susceptibility to dietary obesity was associated with
increased osteoarthritic changes in the knee and impaired
musculoskeletal force generation and motor function compared
with controls. A high-fat diet also induced symptomatic
characteristics of osteoarthritis, including hyperalgesia
and anxiety-like behaviors. Controlling for the effects of
diet and percentage body fat with a multivariate model
revealed a significant association between knee
osteoarthritis severity and serum levels of leptin,
adiponectin, and IL-1α. Physiologic doses of leptin, in the
presence or absence of IL-1α and fatty acids, did not
substantially alter extracellular matrix homeostasis in
healthy cartilage explants. CONCLUSIONS : These results
indicate that diet-induced obesity increases the risk of
symptomatic features of osteoarthritis through changes in
musculoskeletal function and pain-related behaviors.
Furthermore, the independent association of systemic
adipokine levels with knee osteoarthritis severity supports
a role for adipose-associated inflammation in the molecular
pathogenesis of obesity-induced osteoarthritis. Physiologic
levels of leptin do not alter extracellular matrix
homeostasis in healthy cartilage, suggesting that leptin may
be a secondary mediator of osteoarthritis
pathogenesis.},
Language = {eng},
Doi = {10.1186/ar3068},
Key = {fds188625}
}
@article{fds188627,
Author = {JB Catterall and TV Stabler and CR Flannery and VB
Kraus},
Title = {Changes in serum and synovial fluid biomarkers after acute
injury (NCT00332254).},
Journal = {Arthritis research & therapy},
Volume = {12},
Number = {6},
Pages = {R229},
Year = {2010},
ISSN = {1478-6362},
url = {http://dx.doi.org/10.1186/ar3216},
Abstract = {ABSTRACT : INTRODUCTION : Acute trauma involving the
anterior cruciate ligament is believed to be a major risk
factor for the development of post-traumatic osteoarthritis
10 to 20 years post-injury. In this study, to better
understand the early biological changes which occur after
acute injury, we investigated synovial fluid and serum
biomarkers. METHODS : We collected serum from 11 patients
without pre-existing osteoarthritis from a pilot
intervention trial (5 placebo and 6 drug treated) using an
intra-articular interleukin-1 receptor antagonist (IL-1Ra)
therapy, 9 of which also supplied matched synovial fluid
samples at presentation to the clinic after acute knee
injury (mean 15.2 ± 7.2 days) and at the follow-up visit
for reconstructive surgery (mean 47.6 ± 12.4 days). To
exclude patients with pre-existing osteoarthritis (OA), the
study was limited to individuals younger than 40 years of
age (mean 23 ± 3.5) with no prior history of joint symptoms
or trauma. We profiled a total of 21 biomarkers; 20
biomarkers in synovial fluid and 13 in serum with 12
biomarkers measured in both fluids. Biomarkers analyzed in
this study were found to be independent of treatment (P >
0.05) as measured by Mann-Whitney and two-way ANOVA. RESULTS
: We observed significant decreases in synovial fluid (sf)
biomarker concentrations from baseline to follow-up for
sfC-Reactive protein (CRP) (P = 0.039), sflubricin (P =
0.008) and the proteoglycan biomarkers: sfGlycosaminoglycan
(GAG) (P = 0.019), and sfAlanine-Arginine-Glycine-Serine
(ARGS) aggrecan (P = 0.004). In contrast, we observed
significant increases in the collagen biomarkers:
sfC-terminal crosslinked telopeptide type II collagen
(CTxII) (P = 0.012), sfC1,2C (P = 0.039), sfC-terminal
crosslinked telopeptide type I collagen (CTxI) (P = 0.004),
and sfN-terminal telopeptides of type I collagen (NTx) (P =
0.008). The concentrations of seven biomarkers were
significantly higher in synovial fluid than serum suggesting
release from the signal knee: IL-1β (P < 0.0001), fetal
aggrecan FA846 (P = 0.0001), CTxI (P = 0.0002), NTx (P =
0.012), osteocalcin (P = 0.012), Cartilage oligomeric matrix
protein (COMP) (P = 0.0001) and matrix metalloproteinase
(MMP)-3 (P = 0.0001). For these seven biomarkers we found
significant correlations between the serum and synovial
fluid concentrations for only CTxI (P = 0.0002), NTx (P <
0.0001), osteocalcin (P = 0.0002) and MMP-3 (P = 0.038).
CONCLUSIONS : These data strongly suggest that the biology
after acute injury reflects that seen in cartilage explant
models stimulated with pro-inflammatory cytokines, which are
characterized by an initial wave of proteoglycan loss
followed by subsequent collagen loss. As the rise of
collagen biomarkers in synovial fluid occurs within the
first month after injury, and as collagen loss is thought to
be irreversible, very early treatment with agents to either
reduce inflammation and/or reduce collagen loss may have the
potential to reduce the onset of future post-traumatic
osteoarthritis. TRIAL REGISTRATION : The samples used in
this study were derived from a clinical trial NCT00332254
registered with ClinicalTrial.gov.},
Language = {eng},
Doi = {10.1186/ar3216},
Key = {fds188627}
}
@article{fds188645,
Author = {AE Denoble and N Hall and CF Pieper and VB Kraus},
Title = {Patellar skin surface temperature by thermography reflects
knee osteoarthritis severity.},
Journal = {Clinical medicine insights. Arthritis and musculoskeletal
disorders},
Volume = {3},
Pages = {69-75},
Year = {2010},
ISSN = {1179-5441},
url = {http://dx.doi.org/10.4137/CMAMD.S5916},
Abstract = {BACKGROUND: Digital infrared thermal imaging is a means of
measuring the heat radiated from the skin surface. Our goal
was to develop and assess the reproducibility of serial
infrared measurements of the knee and to assess the
association of knee temperature by region of interest with
radiographic severity of knee Osteoarthritis (rOA). METHODS:
A total of 30 women (15 Cases with symptomatic knee OA and
15 age-matched Controls without knee pain or knee OA)
participated in this study. Infrared imaging was performed
with a Meditherm Med2000™ Pro infrared camera. The
reproducibility of infrared imaging of the knee was
evaluated through determination of intraclass correlation
coefficients (ICCs) for temperature measurements from two
images performed 6 months apart in Controls whose knee
status was not expected to change. The average cutaneous
temperature for each of five knee regions of interest was
extracted using WinTes software. Knee x-rays were scored for
severity of rOA based on the global Kellgren-Lawrence
grading scale. RESULTS: The knee infrared thermal imaging
procedure used here demonstrated long-term reproducibility
with high ICCs (0.50-0.72 for the various regions of
interest) in Controls. Cutaneous temperature of the patella
(knee cap) yielded a significant correlation with severity
of knee rOA (R = 0.594, P = 0.02). CONCLUSIONS: The skin
temperature of the patellar region correlated with x-ray
severity of knee OA. This method of infrared knee imaging is
reliable and as an objective measure of a sign of
inflammation, temperature, indicates an interrelationship of
inflammation and structural knee rOA damage.},
Language = {eng},
Doi = {10.4137/CMAMD.S5916},
Key = {fds188645}
}
@article{fds188656,
Author = {VB Kraus and TB Kepler and T Stabler and J Renner and J
Jordan},
Title = {First qualification study of serum biomarkers as indicators
of total body burden of osteoarthritis.},
Journal = {PloS one},
Volume = {5},
Number = {3},
Pages = {e9739},
Year = {2010},
ISSN = {1932-6203},
url = {http://dx.doi.org/10.1371/journal.pone.0009739},
Keywords = {Aged • Arthrography • Biological Markers •
Cartilage • Cohort Studies • Collagen Type II
• Disease Progression • Female • Humans
• Male • Middle Aged • Osteoarthritis •
Phenotype • Rheumatology • metabolism •
metabolism* • methods • pathology •
radiography},
Abstract = {BACKGROUND: Osteoarthritis (OA) is a debilitating chronic
multijoint disease of global proportions. OA presence and
severity is usually documented by x-ray imaging but whole
body imaging is impractical due to radiation exposure, time
and cost. Systemic (serum or urine) biomarkers offer a
potential alternative method of quantifying total body
burden of disease but no OA-related biomarker has ever been
stringently qualified to determine the feasibility of this
approach. The goal of this study was to evaluate the ability
of three OA-related biomarkers to predict various forms or
subspecies of OA and total body burden of disease. RESULTS:
Female participants (461) with clinical hand OA underwent
radiography of hands, hips, knees and lumbar spine; x-rays
were comprehensively scored for OA features of osteophyte
and joint space narrowing. Three OA-related biomarkers,
serum hyaluronan (sHA), cartilage oligomeric matrix protein
(sCOMP), and urinary C-telopeptide of type II collagen
(uCTX2), were measured by ELISA. sHA, sCOMP and uCTX2
correlated positively with total osteophyte burden in models
accounting for demographics (age, weight, height): R(2) =
0.60, R(2) = 0.47, R(2) = 0.51 (all p<10(-6)); sCOMP
correlated negatively with total joint space narrowing
burden: R(2) = 0.69 (p<10(-6)). Biomarkers and demographics
predicted 35-38% of variance in total burden of OA (total
joint space narrowing or osteophyte). Joint size did not
determine the contribution to the systemic biomarker
concentration. Biomarker correlation with disease in the
lumbar spine resembled that in the rest of the skeleton.
CONCLUSIONS: We have suspected that the correlation of
systemic biomarkers with disease has been hampered by the
inability to fully phenotype the burden of OA in a patient.
These results confirm the hypothesis, revealed upon adequate
patient phenotyping, that systemic joint tissue
concentrations of several biomarkers can be quantitative
indicators of specific subspecies of OA and of total body
burden of disease.},
Language = {eng},
Doi = {10.1371/journal.pone.0009739},
Key = {fds188656}
}
@article{fds188633,
Author = {EL Sims and FJ Keefe and VB Kraus and F Guilak and RM Queen and D
Schmitt},
Title = {Racial differences in gait mechanics associated with knee
osteoarthritis.},
Journal = {Aging clinical and experimental research},
Volume = {21},
Number = {6},
Pages = {463-9},
Year = {2009},
Month = {December},
ISSN = {1594-0667},
Keywords = {Adult • African Continental Ancestry Group* • Aged
• Anthropometry • Disability Evaluation •
Educational Status • European Continental Ancestry
Group* • Female • Gait • Humans • Knee
Joint • Male • Middle Aged • Osteoarthritis,
Knee • Range of Motion, Articular • Self Concept
• Severity of Illness Index • ethnology* •
physiology • physiology* • physiopathology •
physiopathology*},
Abstract = {OBJECTIVE: This study examines racial differences in gait
mechanics in persons with knee osteoarthritis and the
influence of anthropometrics, educational level,
radiographic disease severity (rOA), and self-report
measures of pain and disability on racial differences in
gait. METHODS: One hundred seventy five (64 black and 111
white) adults with radiographic knee OA were tested. 3-D
kinematic and kinetic data were collected while subjects
walked at two self-selected speeds (normal and fast).
Anthropometric data, radiographic level of OA, and
self-report measures of pain and disability were also
collected. Gait patterns were compared across groups and
within groups. RESULTS: Black and white subjects did not
differ significantly in radiographic OA. However, blacks
walked significantly more slowly when asked to walk fast. At
the normal speed, blacks had a smaller knee range of motion
and loading rate than whites. Blacks also took longer to
reach their peak maximum ground reaction force than whites.
Within black subjects variations in gait mechanics were
primarily explained by BMI, rOA, selfreported psychological
disability, and pain self-efficacy. In white subjects,
variations in gait mechanics were primarily explained by
weight, age, velocity, psychological disability, and
self-efficacy. CONCLUSIONS: Blacks in this study had a
pattern of gait mechanics generally associated with high
levels of osteoarthritis, though they did not differ
significantly in rOA from whites. The variability in gait
patterns exhibited by blacks was most strongly related to
variance in walking speed, anthropometrics, and perceived
physical ability. Taken together, these results suggest that
race is an important factor that must be considered in the
treatment and study of osteoarthritis.},
Language = {eng},
Key = {fds188633}
}
@article{fds188659,
Author = {VB Kraus and S Feng and S Wang and S White and M Ainslie and A Brett and A
Holmes, HC Charles},
Title = {Trabecular morphometry by fractal signature analysis is a
novel marker of osteoarthritis progression.},
Journal = {Arthritis and rheumatism},
Volume = {60},
Number = {12},
Pages = {3711-22},
Year = {2009},
Month = {December},
ISSN = {0004-3591},
url = {http://dx.doi.org/10.1002/art.25012},
Keywords = {Age Factors • Disease Progression • Female •
Fractals • Humans • Image Processing,
Computer-Assisted • Knee Joint • Male •
Osteoarthritis, Knee • Osteophyte • Predictive
Value of Tests • ROC Curve • Tibia • methods*
• pathology • pathology* • physiopathology
• radiography*},
Abstract = {OBJECTIVE: To evaluate the effectiveness of using
subchondral bone texture observed on a radiograph taken at
baseline to predict progression of knee osteoarthritis (OA)
over a 3-year period. METHODS: A total of 138 participants
in the Prediction of Osteoarthritis Progression study were
evaluated at baseline and after 3 years. Fractal signature
analysis (FSA) of the medial subchondral tibial plateau was
performed on fixed flexion radiographs of 248 nonreplaced
knees, using a commercially available software tool. OA
progression was defined as a change in joint space narrowing
(JSN) or osteophyte formation of 1 grade according to a
standardized knee atlas. Statistical analysis of fractal
signatures was performed using a new model based on
correlating the overall shape of a fractal dimension curve
with radius. RESULTS: Fractal signature of the medial tibial
plateau at baseline was predictive of medial knee JSN
progression (area under the curve [AUC] 0.75, of a receiver
operating characteristic curve) but was not predictive of
osteophyte formation or progression of JSN in the lateral
compartment. Traditional covariates (age, sex, body mass
index, knee pain), general bone mineral content, and joint
space width at baseline were no more effective than random
variables for predicting OA progression (AUC 0.52-0.58). The
predictive model with maximum effectiveness combined fractal
signature at baseline, knee alignment, traditional
covariates, and bone mineral content (AUC 0.79).
CONCLUSIONS: We identified a prognostic marker of OA that is
readily extracted from a plain radiograph using FSA.
Although the method needs to be validated in a second
cohort, our results indicate that the global shape approach
to analyzing these data is a potentially efficient means of
identifying individuals at risk of knee OA
progression.},
Language = {eng},
Doi = {10.1002/art.25012},
Key = {fds188659}
}
@article{fds188651,
Author = {S Addison and RE Coleman and S Feng and G McDaniel and VB
Kraus},
Title = {Whole-body bone scintigraphy provides a measure of the
total-body burden of osteoarthritis for the purpose of
systemic biomarker validation.},
Journal = {Arthritis and rheumatism},
Volume = {60},
Number = {11},
Pages = {3366-73},
Year = {2009},
Month = {November},
ISSN = {0004-3591},
url = {http://dx.doi.org/10.1002/art.24856},
Keywords = {Adult • Aged • Aged, 80 and over • Biological
Markers • Extracellular Matrix Proteins • Female
• Glycoproteins • Humans • Knee Joint •
Male • Middle Aged • Osteoarthritis, Knee •
Radionuclide Imaging • Reproducibility of Results
• Severity of Illness Index • Synovial Fluid
• Whole Body Imaging • blood • blood* •
metabolism • methods* • radionuclide imaging
• radionuclide imaging*},
Abstract = {OBJECTIVE: To evaluate the association of serum and synovial
fluid cartilage oligomeric matrix protein (COMP) with
systemic and local measures of osteoarthritis (OA) activity
by bone scintigraphy. METHODS: Samples of serum and knee
joint synovial fluid (275 knees) were obtained from 159
patients with symptomatic OA of at least 1 knee. Bone
scintigraphy using (99m)Tc-labeled methylene diphosphonate
was performed, and early-phase knee scans and late-phase
whole-body bone scans of 15 additional joint sites were
scored semiquantitatively. To control for within-subject
correlations of knee data, generalized linear modeling was
used in the correlation of the bone scan scores with the
COMP levels. Principal components analysis was used to
explore the contribution of each joint site to the variance
in serum COMP levels. RESULTS: The correlation between
synovial fluid and serum COMP levels was significant (r =
0.206, P = 0.006). Synovial fluid COMP levels correlated
most strongly with the early-phase knee bone scan scores (P
= 0.0003), even after adjustment for OA severity according
to the late-phase bone scan scores (P = 0.015), as well as
synovial fluid volumes (P < 0.0001). Serum COMP levels
correlated with the total-body bone scan scores (r = 0.188,
P = 0.018) and with a factor composed of the bone scan
scores in the shoulders, spine, lateral knees, and
sacroiliac joints (P = 0.0004). CONCLUSIONS: Synovial fluid
COMP levels correlated strongly with 2 indicators of knee
joint inflammation: early-phase bone scintigraphic findings
and synovial fluid volume. Serum COMP levels correlated with
total-body joint disease severity as determined by
late-phase bone scintigraphy, supporting the hypothesis that
whole-body bone scintigraphy is a means of quantifying the
total-body burden of OA for systemic biomarker
validation.},
Language = {eng},
Doi = {10.1002/art.24856},
Key = {fds188651}
}
@article{fds188663,
Author = {MB Nebel and EL Sims and FJ Keefe and VB Kraus and F Guilak and DS
Caldwell, JJ Pells and R Queen and D Schmitt},
Title = {The relationship of self-reported pain and functional
impairment to gait mechanics in overweight and obese persons
with knee osteoarthritis.},
Journal = {Archives of physical medicine and rehabilitation},
Volume = {90},
Number = {11},
Pages = {1874-9},
Year = {2009},
Month = {November},
ISSN = {1532-821X},
url = {http://dx.doi.org/10.1016/j.apmr.2009.07.010},
Keywords = {Disability Evaluation* • Disabled Persons • Female
• Gait • Humans • Male • Middle Aged
• Obesity • Osteoarthritis, Knee •
Overweight* • Pain • Pain Measurement •
Regression Analysis • Self Disclosure •
complications • etiology* • physiology* •
physiopathology*},
Abstract = {OBJECTIVE: To examine the degree to which 2 commonly used
measures of pain and disability, the Arthritis Impact
Measurement Scales (AIMS) and the Western Ontario and
McMaster Universities Osteoarthritis Index (WOMAC), relate
to objective gait measurements. METHODS: A descriptive study
of the influence of self-reported pain and perceived
functional impairment on gait mechanics in osteoarthritic
adults. METHODS: A university clinical research laboratory.
METHODS: Overweight/obese adults with radiographic knee
osteoarthritis (OA) as well as pain and disability
associated with the disease (N=179). METHODS: Not
applicable. METHODS: The AIMS and WOMAC were administered to
determine self-report measures of pain and disability.
Speed, stride length, support time, knee angle, and peak
vertical force (PVF) were determined from 3-dimensional
kinematic and kinetic data collected on subjects walking at
self-selected normal and fast speeds. Anthropometric data
and radiographic levels of OA were also collected. RESULTS:
Pearson correlation analysis showed that the AIMS physical
disability score was inversely correlated with speed, stride
length, and knee range of motion at both speeds and PVF at
the fast speed. The WOMAC function score was inversely
correlated with speed and stride length at both speeds and
with PVF at fast speed. The WOMAC pain score was inversely
correlated with speed and PVF at the fast speed. Regression
analysis revealed that the AIMS physical disability score
and body mass index accounted for the greatest variation in
speed at the normal speed. Overall, AIMS physical disability
and WOMAC function explained a larger proportion of variance
in gait mechanics than radiographic measures of OA disease
severity. CONCLUSIONS: Taken together, the results suggest
that the AIMS physical disability and WOMAC function scores
are associated with some important measures of gait
impairment.},
Language = {eng},
Doi = {10.1016/j.apmr.2009.07.010},
Key = {fds188663}
}
@article{fds188657,
Author = {TM Griffin and JL Huebner and VB Kraus and F Guilak},
Title = {Extreme obesity due to impaired leptin signaling in mice
does not cause knee osteoarthritis.},
Journal = {Arthritis and rheumatism},
Volume = {60},
Number = {10},
Pages = {2935-44},
Year = {2009},
Month = {October},
ISSN = {0004-3591},
url = {http://dx.doi.org/10.1002/art.24854},
Keywords = {Adiposity • Animals • Biomechanics • Body
Composition • Bone Density • Bone and Bones •
Cytokines • Disease Models, Animal • Female •
Inflammation • Joints • Leptin • Mice •
Mice, Inbred C57BL • Mice, Knockout • Obesity,
Morbid • Osteoarthritis • Receptors, Leptin •
Risk Factors • Signal Transduction • blood •
complications* • etiology • etiology* •
genetics • metabolism • metabolism* •
pathology • physiology • physiology*},
Abstract = {OBJECTIVE: To test the hypothesis that obesity resulting
from deletion of the leptin gene or the leptin receptor gene
results in increased knee osteoarthritis (OA), systemic
inflammation, and altered subchondral bone morphology.
METHODS: Leptin-deficient (ob/ob) and leptin
receptor-deficient (db/db) female mice compared with
wild-type mice were studied, to document knee OA via
histopathology. The levels of serum proinflammatory and
antiinflammatory cytokines were measured using a multiplex
bead immunoassay. Cortical and trabecular subchondral bone
changes were documented by microfocal computed tomography,
and body composition was quantified by dual x-ray
absorptiometry. RESULTS: Adiposity was increased by
approximately 10-fold in ob/ob and db/db mice compared with
controls, but it was not associated with an increased
incidence of knee OA. Serum cytokine levels were unchanged
in ob/ob and db/db mice relative to controls, except for the
level of cytokine-induced neutrophil chemoattractant
(keratinocyte chemoattractant; murine analog of
interleukin-8), which was elevated. Leptin impairment was
associated with reduced subchondral bone thickness and
increased relative trabecular bone volume in the tibial
epiphysis. CONCLUSIONS: Extreme obesity due to impaired
leptin signaling induced alterations in subchondral bone
morphology without increasing the incidence of knee OA.
Systemic inflammatory cytokine levels remained largely
unchanged in ob/ob and db/db mice. These findings suggest
that body fat, in and of itself, may not be a risk factor
for joint degeneration, because adiposity in the absence of
leptin signaling is insufficient to induce systemic
inflammation and knee OA in female C57BL/6J mice. These
results imply a pleiotropic role of leptin in the
development of OA by regulating both the skeletal and immune
systems.},
Language = {eng},
Doi = {10.1002/art.24854},
Key = {fds188657}
}
@article{fds188647,
Author = {KD Allen and TM Griffin and RM Rodriguiz and WC Wetsel and VB Kraus and JL
Huebner, LM Boyd and LA Setton},
Title = {Decreased physical function and increased pain sensitivity
in mice deficient for type IX collagen.},
Journal = {Arthritis and rheumatism},
Volume = {60},
Number = {9},
Pages = {2684-93},
Year = {2009},
Month = {September},
ISSN = {0004-3591},
url = {http://dx.doi.org/10.1002/art.24783},
Keywords = {Animals • Arthralgia • Biomechanics •
Collagen Type IX • Disease Models, Animal • Female
• Gait • Hyaluronic Acid • Intervertebral
Disk • Male • Mice • Mice, Inbred C57BL
• Mice, Knockout • Models, Genetic • Motor
Activity • Osteoarthritis • Severity of Illness
Index • blood • deficiency* • genetics*
• metabolism • pathology • physiology •
physiology* • physiopathology*},
Abstract = {OBJECTIVE: In mice with Col9a1 gene inactivation
(Col9a1(-/-)), osteoarthritis (OA) and intervertebral disc
degeneration develop prematurely. The aim of this study was
to investigate Col9a1(-/-) mice for functional and
symptomatic changes that may be associated with these
pathologies. METHODS: Col9a1(-/-) and wild-type mice were
investigated for reflexes, functional impairment (beam
walking, pole climbing, wire hang, grip strength),
sensorimotor skills (rotarod), mechanical sensitivity (von
Frey hair), and thermal sensitivity (hot plate/tail flick).
Gait was also analyzed to determine velocity, stride
frequency, symmetry, percentage stance time, stride length,
and step width. Postmortem, sera obtained from the mice were
analyzed for hyaluronan, and their knees and spines were
graded histologically for degeneration. RESULTS: Col9a1(-/-)
mice had compensatory gait changes, increased mechanical
sensitivity, and impaired physical ability. Col9a1(-/-) mice
ambulated with gaits characterized by increased percentage
stance times and shorter stride lengths. These mice also had
heightened mechanical sensitivity and were deficient in
contact righting, wire hang, rotarod, and pole climbing
tasks. Male Col9a1(-/-) mice had the highest mean serum
hyaluronan levels and strong histologic evidence of
cartilage erosion. Intervertebral disc degeneration was also
detected, with Col9a1(-/-) mice having an increased
incidence of disc tears. CONCLUSIONS: These data describe a
Col9a1(-/-) behavioral phenotype characterized by altered
gait, increased mechanical sensitivity, and impaired
function. These gait and functional differences suggest that
Col9a1(-/-) mice select locomotive behaviors that limit
joint loads. The nature and magnitude of behavioral changes
were largest in male mice, which also had the greatest
evidence of knee degeneration. These findings suggest that
Col9a1(-/-) mice present behavioral changes consistent with
anatomic signs of OA and intervertebral disc
degeneration.},
Language = {eng},
Doi = {10.1002/art.24783},
Key = {fds188647}
}
@article{fds188654,
Author = {MP Hellio Le Graverand and RJ Buck and BT Wyman and E Vignon and SA
Mazzuca, KD Brandt and M Piperno and HC Charles and M Hudelmaier and DJ
Hunter, C Jackson and VB Kraus and TM Link and S Majumdar and PV Prasad and TJ Schnitzer and A Vaz and W Wirth and F Eckstein},
Title = {Subregional femorotibial cartilage morphology in
women--comparison between healthy controls and participants
with different grades of radiographic knee
osteoarthritis.},
Journal = {Osteoarthritis and cartilage / OARS, Osteoarthritis Research
Society},
Volume = {17},
Number = {9},
Pages = {1177-85},
Year = {2009},
Month = {September},
ISSN = {1522-9653},
url = {http://dx.doi.org/10.1016/j.joca.2009.03.008},
Keywords = {Adult • Aged • Cartilage, Articular •
Cross-Sectional Studies • Female • Femur •
Humans • Knee Joint • Longitudinal Studies •
Magnetic Resonance Imaging • Middle Aged •
Osteoarthritis, Knee • Statistics as Topic • Tibia
• methods • pathology • pathology* •
radiography},
Abstract = {OBJECTIVE: To identify subregional differences in
femorotibial cartilage morphology between healthy controls
and women with different grades of radiographic knee
osteoarthritis (OA). METHODS: 158 women aged > or =40 years
were studied. Weight-bearing extended anterior-posterior
(AP) and Lyon schuss radiographs were obtained and the
Kellgren Lawrence grade (KLG) determined. 97 women had a
body mass index (BMI)< or =28, no symptoms, and were AP
KLG0. 61 women had a BMI> or =30, symptoms in the target
knee, and mild (KLG2=31) to moderate (KLG3=30) medial
femorotibial radiographic OA in the AP views. Coronal
spoiled gradient echo water excitation sequences were
acquired at 3.0 Tesla. Total plate and regional measures of
cartilage morphology of the weight-bearing femorotibial
joint were quantified. RESULTS: KLG2 participants displayed,
on average, thicker cartilage than healthy controls in the
medial femorotibial compartment (particularly anterior
subregion of the medial tibia (MT) and peripheral [external,
internal] subregions of the medial femur), and in the
lateral femur. KLG3 participants displayed significantly
thinner cartilage than KLG0 participants in the medial
weight-bearing femur (central subregion), in the external
subregion of the MT, and in the internal subregion of the
lateral tibia. These differences were generally unaffected
when possible effects of demographic covariates were
considered. CONCLUSIONS: The results indicate that in
femorotibial OA regional cartilage thickening and thinning
may occur, dependent on the (radiographic) disease status of
the joint. These changes appear to display a heterogeneous
spatial pattern, where certain subregions are more strongly
affected than others.},
Language = {eng},
Doi = {10.1016/j.joca.2009.03.008},
Key = {fds188654}
}
@article{fds188612,
Author = {WP Maksymowych and R Landewé and PP Tak and CJ Ritchlin and M
Ostergaard, PJ Mease and H El-Gabalawy and P Garnero and DD Gladman and O Fitzgerald and D Aletaha and VP Bykerk and JM Bathon and SW Syversen and M Boers and P Geusens and RD Inman and VB Kraus and TK Kvien and WJ Taylor and GA Wells and D van der Heijde},
Title = {Reappraisal of OMERACT 8 draft validation criteria for a
soluble biomarker reflecting structural damage endpoints in
rheumatoid arthritis, psoriatic arthritis, and
spondyloarthritis: the OMERACT 9 v2 criteria.},
Journal = {The Journal of rheumatology},
Volume = {36},
Number = {8},
Pages = {1785-91},
Year = {2009},
Month = {August},
ISSN = {0315-162X},
url = {http://dx.doi.org/10.3899/jrheum.090346},
Keywords = {Arthritis • Arthritis, Psoriatic • Arthritis,
Rheumatoid • Biological Markers • Humans •
Joints • Predictive Value of Tests •
Reproducibility of Results • Spondylarthritis •
blood • blood* • pathology •
pathology*},
Abstract = {OBJECTIVE: A draft set of criteria for the validation of
soluble biomarkers reflecting damage endpoints was proposed
at OMERACT 8. At OMERACT 9 we aimed to scrutinize the
necessity for each of these criteria according to the
objectives of the working group. METHODS: The OMERACT 8
draft criteria and the principle objectives of the
validation process were clarified at a meeting of the
working group in London, December 2007. A new framework was
proposed after the following steps were conducted: (A) A
systematic review of the literature focusing on the draft
criteria and a preselected group of biomarkers (MMP3,
CTX-II, RANKL, OPG, CTX-I) followed by a Delphi consensus
exercise addressing the importance of individual criteria
and identification of omissions in the draft set. (B) Formal
debate as well as group discussion centered on the key
arguments for inclusion/exclusion of specific criteria. (C)
Onsite interactive electronic voting on the importance of
specific criteria. The framework was presented and discussed
at OMERACT 9 in both breakout and plenary sessions followed
by a vote on its acceptance. RESULTS: The objectives of
rheumatoid arthritis, psoriatic arthritis, and ankylosing
spondylitis biomarkers in relation to their predictive
validity for damage endpoints was clarified and supported by
OMERACT 9 participants. The OMERACT 8 draft validation
criteria were reformulated into an essential category
focused on criteria addressing the OMERACT Filter elements
of discrimination (incorporating truth) and feasibility, and
a desirable but nonessential category of other criteria
addressing truth. This revised draft set was endorsed by
participants at OMERACT 9. CONCLUSIONS: A revised set of
validation criteria has been drafted by consensus at OMERACT
9 that focuses on the performance characteristics of
biomarker assays, the importance of addressing potential
confounders, and the essential requirement for clinical
validation studies.},
Language = {eng},
Doi = {10.3899/jrheum.090346},
Key = {fds188612}
}
@article{fds188640,
Author = {JL Huebner and KA Johnson and VB Kraus and RA Terkeltaub},
Title = {Transglutaminase 2 is a marker of chondrocyte hypertrophy
and osteoarthritis severity in the Hartley guinea pig model
of knee OA.},
Journal = {Osteoarthritis and cartilage / OARS, Osteoarthritis Research
Society},
Volume = {17},
Number = {8},
Pages = {1056-64},
Year = {2009},
Month = {August},
ISSN = {1522-9653},
url = {http://dx.doi.org/10.1016/j.joca.2009.02.015},
Keywords = {Animals • Arthritis, Experimental • Biological
Markers • Cartilage, Articular • Chondrocytes
• GTP-Binding Proteins • Gene Expression •
Guinea Pigs • Immunohistochemistry •
Osteoarthritis, Knee • Severity of Illness Index •
Transglutaminases • genetics • metabolism •
metabolism* • pathology*},
Abstract = {OBJECTIVE: The transglutaminase (TG) isoenzyme TG2, which
catalyzes protein cross-linking via transamidation,
influences healing phenotype in multiple forms of tissue
injury. Moreover, TG2 knockout suppresses cartilage
destruction but promotes osteophyte formation in
instability-induced mouse knee osteoarthritis (OA). TG2 is
marker of growth plate chondrocyte hypertrophy. Moreover,
TG2 secreted by chondrocytes acts in part by promoting
chondrocyte maturation to hypertrophy, a differentiation
state linked with MMP-13 expression and disease progression
in OA. Moreover, glucosamine, which is currently under
investigation as an OA therapy, binds and inhibits TG2.
Here, we examined TG2 as a potential marker of cartilage
hypertrophy in the spontaneous guinea pig model of OA.
METHODS: Synovial fluid ELISA and cartilage
Immunohistochemistry and quantitative Reverse
transcription-polymerase chain reaction (RT-PCR), were used
to examine TG2 expression and TG transamidation-catalyzed
isopeptide bonds. RESULTS: TG isopeptide bonds and TG2 were
most abundant in articular cartilage in early knee OA. TG2
expression was robust at sites of early but not established
osteophytes. Synovial fluid TG2 correlated with knee OA
total histological score (r=0.47, P=0.01), as did medial
tibial plateau cartilage TG2 mRNA (r=1.0, P=0.003). At 12
months of age, medial tibial plateau cartilage TG2 mRNA
expression rose markedly in association with elevated type X
collagen, as well as ADAMTS-5, and MMP-13 expression,
changes not shared in age-matched Strain 13 guinea pigs that
are less susceptible to knee OA. CONCLUSIONS: Hartley guinea
pig knee TG2 expression associates with enhanced articular
chondrocyte hypertrophy and is a biomarker of OA
severity.},
Language = {eng},
Doi = {10.1016/j.joca.2009.02.015},
Key = {fds188640}
}
@article{fds188641,
Author = {WP Maksymowych and O Fitzgerald and GA Wells and DD Gladman and R
Landewé, M Ostergaard and WJ Taylor and R Christensen and PP Tak and M
Boers, SW Syversen and JM Bathon and CJ Ritchlin and PJ Mease and VP
Bykerk, P Garnero and P Geusens and H El-Gabalawy and D Aletaha and RD
Inman, VB Kraus and TK Kvien and D van der Heijde},
Title = {Proposal for levels of evidence schema for validation of a
soluble biomarker reflecting damage endpoints in rheumatoid
arthritis, psoriatic arthritis, and ankylosing spondylitis,
and recommendations for study design.},
Journal = {The Journal of rheumatology},
Volume = {36},
Number = {8},
Pages = {1792-9},
Year = {2009},
Month = {August},
ISSN = {0315-162X},
url = {http://dx.doi.org/10.3899/jrheum090347},
Keywords = {Arthritis • Arthritis, Psoriatic • Arthritis,
Rheumatoid • Biological Markers • Evidence-Based
Medicine • Humans • Joints • Longitudinal
Studies • Predictive Value of Tests •
Reproducibility of Results • Spondylitis, Ankylosing
• blood • blood* • pathology •
pathology* • standards*},
Abstract = {OBJECTIVE: At OMERACT 8 a framework for levels of evidence
was proposed for the validation of biomarkers as surrogate
outcome measures. We aimed to adapt this scheme in order to
apply it in the setting of soluble biomarkers proposed to
replace the measurement of damage endpoints in rheumatoid
arthritis (RA), psoriatic arthritis (PsA), and ankylosing
spondylitis (AS). We also aimed to generate consensus on
minimum standards for the design of longitudinal studies
aimed at validating biomarkers. METHODS: Before the meeting,
the Soluble Biomarker Working Group prepared a preliminary
framework and discussed various models for association and
prediction related to the statistical strength domain. In
addition, 3 Delphi exercises addressing longitudinal study
design for RA, PsA, and AS were conducted within the working
group and members of the Assessments in SpondyloArthritis
International Society (ASAS) and the Group for Research and
Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA).
This formed the basis for discussions among OMERACT 9
participants. RESULTS: The proposed framework was accepted
by consensus. In the study design domain a requirement for
both prospective observational studies and randomized
controlled trials (RCT) in different drug classes was noted.
A template for determining the level of statistical strength
was proposed. The addition of a new domain on biomarker
assay performance was considered essential, and participants
suggested that for any biomarker this domain should be
addressed first, i.e., before starting clinical validation
studies. Participants agreed on most elements of a
longitudinal study design template. Where consensus was
lacking the working group has drafted solutions that
constitute a basis for prospective validation studies.
CONCLUSIONS: The OMERACT 9 Soluble Biomarker Group has
successfully formulated a levels of evidence scheme and a
study design template that will provide guidance to conduct
validation studies in the setting of soluble biomarkers
proposed to replace the measurement of damage endpoints in
RA, PsA, and AS.},
Language = {eng},
Doi = {10.3899/jrheum090347},
Key = {fds188641}
}
@article{fds188624,
Author = {EL Sims and JM Carland and FJ Keefe and VB Kraus and F Guilak and D
Schmitt},
Title = {Sex differences in biomechanics associated with knee
osteoarthritis.},
Journal = {Journal of women & aging},
Volume = {21},
Number = {3},
Pages = {159-70},
Year = {2009},
Month = {July},
ISSN = {1540-7322},
url = {http://dx.doi.org/10.1080/08952840903054856},
Keywords = {Adult • Aged • Biomechanics • Female •
Humans • Imaging, Three-Dimensional • Male •
Middle Aged • Osteoarthritis, Knee • Prevalence
• Severity of Illness Index • Sex Distribution
• epidemiology* • physiopathology*},
Abstract = {Osteoarthritis of the knee is seen more frequently in
females than males. However, few studies have examined the
interplay of gender, gait mechanics, pain, and disability in
persons with osteoarthritis. This study examines the
influence of anthropometrics, radiographic disease severity,
pain, and disability on gender differences in gait mechanics
in patients with knee osteoarthritis. Gait mechanics for 26
men and 30 women were collected using 3-D kinematics and
kinetics. Women had a significantly lower knee adduction
moment than men and a significantly higher stride frequency.
Within female subjects, variations in gait mechanics were
primarily explained by weight, BMI, pain, and disability. In
males, variations in gait mechanics were primarily explained
by age and disability.},
Language = {eng},
Doi = {10.1080/08952840903054856},
Key = {fds188624}
}
@article{fds188643,
Author = {AE Nelson and F Fang and XA Shi and VB Kraus and T Stabler and JB Renner and TA Schwartz and CG Helmick and JM Jordan},
Title = {Failure of serum transforming growth factor-beta (TGF-beta1)
as a biomarker of radiographic osteoarthritis at the knee
and hip: a cross-sectional analysis in the Johnston County
Osteoarthritis Project.},
Journal = {Osteoarthritis and cartilage / OARS, Osteoarthritis Research
Society},
Volume = {17},
Number = {6},
Pages = {772-6},
Year = {2009},
Month = {June},
ISSN = {1522-9653},
url = {http://dx.doi.org/10.1016/j.joca.2008.11.010},
Keywords = {Biological Markers • Cross-Sectional Studies •
Female • Hip Joint • Humans • Knee Joint
• Male • Middle Aged • Osteoarthritis, Hip
• Osteoarthritis, Knee • Transforming Growth
Factor beta1 • Weight-Bearing • blood •
blood* • ethnology • metabolism* •
radiography},
Abstract = {OBJECTIVE: To assess associations between serum transforming
growth factor-beta (TGF-beta1) and radiographic knee and hip
osteoarthritis (rOA) in African American (AA) and White men
and women. METHODS: Baseline data from 330 participants in
the Johnston County Osteoarthritis Project were used in the
analysis. Radiographs were scored with the Kellgren-Lawrence
scale and rOA defined as grade> or =2. Individual
radiographic features (IRFs) were rated 0-3. TGF-beta1 was
measured using a sandwich enzyme-linked immunosorbent assay
(ELISA). General linear models were used to estimate
associations between lnTGF-beta1 and rOA presence,
laterality or severity, and IRF presence and severity,
adjusting for age, gender, race and body mass index.
Interactions by race and gender were considered significant
at P<0.1. RESULTS: Mean lnTGF-beta1 levels were higher among
AAs compared to Whites, and among women compared to men
(P<0.009). Mean lnTGF-beta1 levels were higher in those with
knee osteophytes (OST), but this association was not
significant after adjustment. There were no other
significant differences in mean lnTGF-beta1 levels by
presence, laterality, or severity of knee or hip rOA or
IRFs. No race or gender interactions were identified,
although a borderline significant association between
lnTGF-beta1 and knee OST was seen among AAs (P<0.06).
CONCLUSIONS: Although serum TGF-beta1 varied by race and
gender and several rOA variables, there were no independent
significant associations with presence, laterality, or
severity of knee or hip rOA by K-L grade or IRFs, suggesting
that serum TGF-beta1 is unlikely to be useful as a
stand-alone biomarker in OA studies. A possible association
between TGF-beta1 and OST in AAs cannot be
excluded.},
Language = {eng},
Doi = {10.1016/j.joca.2008.11.010},
Key = {fds188643}
}
@article{fds188637,
Author = {J Cibere and H Zhang and P Garnero and AR Poole and T Lobanok and T Saxne and VB Kraus and A Way and A Thorne and H Wong and J Singer and J Kopec and A
Guermazi, C Peterfy and S Nicolaou and PL Munk and JM
Esdaile},
Title = {Association of biomarkers with pre-radiographically defined
and radiographically defined knee osteoarthritis in a
population-based study.},
Journal = {Arthritis and rheumatism},
Volume = {60},
Number = {5},
Pages = {1372-80},
Year = {2009},
Month = {May},
ISSN = {0004-3591},
url = {http://dx.doi.org/10.1002/art.24473},
Keywords = {Adult • Aged • Biological Markers •
Calcium-Binding Proteins • Cartilage, Articular •
Chondroitin Sulfates • Collagen Type I • Collagen
Type II • Extracellular Matrix Proteins • Female
• Glycoproteins • Humans • Hyaluronic Acid
• Magnetic Resonance Imaging • Male • Middle
Aged • Osteoarthritis, Knee • Peptides •
analysis* • blood • diagnosis* • radiography
• urine},
Abstract = {OBJECTIVE: To evaluate 10 biomarkers in magnetic resonance
imaging (MRI)-determined, pre-radiographically defined
osteoarthritis (pre-ROA) and radiographically defined OA
(ROA) in a population-based cohort of subjects with
symptomatic knee pain. METHODS: Two hundred one white
subjects with knee pain, ages 40-79 years, were classified
into OA subgroups according to MRI-based cartilage (MRC)
scores (range 0-4) and Kellgren/Lawrence (K/L) grades of
radiographic severity (range 0-4): no OA (MRC score 0, K/L
grade<2), pre-ROA (MRC score>or=1, K/L grade<2), or ROA (MRC
score>or=1, K/L grade>or=2). Urine and serum samples were
assessed for levels of the following biomarkers: urinary
biomarkers C-telopeptide of type II collagen (uCTX-II), type
II and types I and II collagen cleavage neoepitopes (uC2C
and uC1,2C, respectively), and N-telopeptide of type I
collagen, and serum biomarkers sC1,2C, sC2C, C-propeptide of
type II procollagen (sCPII), chondroitin sulfate 846
epitope, cartilage oligomeric matrix protein, and hyaluronic
acid. Multicategory logistic regression was performed to
evaluate the association of OA subgroup with individual
biomarker levels and biomarker ratios, adjusted for age,
sex, and body mass index. RESULTS: The risk of ROA versus no
OA increased with increasing levels of uCTX-II (odds ratio
[OR] 3.12, 95% confidence interval [95% CI] 1.35-7.21), uC2C
(OR 2.13, 95% CI 1.04-4.37), and uC1,2C (OR 2.07, 95% CI
1.06-4.04), and was reduced in association with high levels
of sCPII (OR 0.53, 95% CI 0.30-0.94). The risk of pre-ROA
versus no OA increased with increasing levels of uC2C (OR
2.06, 95% CI 1.05-4.01) and uC1,2C (OR 2.06, 95% CI
1.12-3.77). The ratios of type II collagen degradation
markers to collagen synthesis markers were better than
individual biomarkers at differentiating the OA subgroups,
e.g., the ratio of [uCTX-II][uC1,2C] to sCPII was associated
with a risk of ROA versus no OA of 3.47 (95% CI 1.34-9.03)
and a risk of pre-ROA versus no OA of 2.56 (95% CI
1.03-6.40). CONCLUSIONS: Different cartilage degradation
markers are associated with pre-ROA than are associated with
ROA, indicating that their use as diagnostic markers depends
on the stage of OA. Biomarker ratios contrasting cartilage
degradation with cartilage synthesis are better able to
differentiate OA stages compared with levels of the
individual markers.},
Language = {eng},
Doi = {10.1002/art.24473},
Key = {fds188637}
}
@article{fds188658,
Author = {TJ Somers and FJ Keefe and JJ Pells and KE Dixon and SJ Waters and PA
Riordan, JA Blumenthal and DC McKee and L LaCaille and JM Tucker and D
Schmitt, DS Caldwell and VB Kraus and EL Sims and RA Shelby, JR
Rice},
Title = {Pain catastrophizing and pain-related fear in osteoarthritis
patients: relationships to pain and disability.},
Journal = {Journal of pain and symptom management},
Volume = {37},
Number = {5},
Pages = {863-72},
Year = {2009},
Month = {May},
ISSN = {1873-6513},
url = {http://dx.doi.org/10.1016/j.jpainsymman.2008.05.009},
Keywords = {Activities of Daily Living* • Anxiety •
Comorbidity • Disability Evaluation* • Fear*
• Female • Humans • Male • Middle Aged
• North Carolina • Osteoarthritis, Knee •
Pain • Risk Assessment • Risk Factors •
diagnosis • epidemiology • epidemiology* •
methods • psychology},
Abstract = {This study examined the degree to which pain catastrophizing
and pain-related fear explain pain, psychological
disability, physical disability, and walking speed in
patients with osteoarthritis (OA) of the knee. Participants
in this study were 106 individuals diagnosed as having OA of
at least one knee, who reported knee pain persisting for six
months or longer. Results suggest that pain catastrophizing
explained a significant proportion (all Ps < or = 0.05) of
variance in measures of pain (partial r(2) [pr(2)] = 0.10),
psychological disability (pr(2) = 0.20), physical disability
(pr(2) = 0.11), and gait velocity at normal (pr(2) = 0.04),
fast (pr(2) = 0.04), and intermediate speeds (pr(2) = 0.04).
Pain-related fear explained a significant proportion of the
variance in measures of psychological disability (pr(2) =
0.07) and walking at a fast speed (pr(2) = 0.05). Pain
cognitions, particularly pain catastrophizing, appear to be
important variables in understanding pain, disability, and
walking at normal, fast, and intermediate speeds in knee OA
patients. Clinicians interested in understanding variations
in pain and disability in this population may benefit by
expanding the focus of their inquiries beyond traditional
medical and demographic variables to include an assessment
of pain catastrophizing and pain-related
fear.},
Language = {eng},
Doi = {10.1016/j.jpainsymman.2008.05.009},
Key = {fds188658}
}
@article{fds188646,
Author = {MF Shamji and KD Allen and S So and L Jing and SB Adams Jr and R Schuh and J
Huebner, VB Kraus and AH Friedman and LA Setton and WJ
Richardson},
Title = {Gait abnormalities and inflammatory cytokines in an
autologous nucleus pulposus model of radiculopathy.},
Journal = {Spine},
Volume = {34},
Number = {7},
Pages = {648-54},
Year = {2009},
Month = {April},
ISSN = {1528-1159},
url = {http://dx.doi.org/10.1097/BRS.0b013e318197f013},
Keywords = {Animals • Autoantibodies • Autoantigens •
Autoimmune Diseases • Cytokines • Disease Models,
Animal • Fibrocartilage • Ganglia, Spinal •
Hyperalgesia • Inflammation • Inflammation
Mediators • Intervertebral Disk • Intervertebral
Disk Displacement • Lameness, Animal • Lumbar
Vertebrae • Male • Radiculopathy • Rats
• Rats, Sprague-Dawley • Transplantation,
Autologous • analysis • blood • blood* •
etiology • immunology • immunology* •
metabolism • methods • pathology •
physiopathology • physiopathology*},
Abstract = {METHODS: The authors investigated gait abnormalities and
mechanical hypersensitivity associated with invertebral disc
herniation in a rat model of radiculopathy. Further
evaluation involved assessing how nucleus pulposus (NP)
injury affected systemic cytokine expression and molecular
changes at the dorsal root ganglion (DRG). OBJECTIVE: The
objective of this work was to describe the gait and
behavioral changes in an animal model of disc-herniation
induced radiculopathy. A second objective included examining
how these functional changes correlated with
neuroinflammation and autoreactive lymphocyte immune
activation. BACKGROUND: Animal models of radiculopathy
describe demyelination, slowed nerve conduction, and
heightened pain sensitivity after application of autologous
NP to the DRG. The quantitative impact of disc herniation on
animal locomotion has not been investigated. Further, while
local inflammation occurs at the injury site, the role of
autoimmune cytokines reactive against previously
immune-sequestered NP requires investigation. METHODS:
NP-treated animals (n = 16) received autologous tail NP
placed onto the L5 DRG exposed by unilateral facetectomy,
and control animals (n = 16) underwent exposure only. At
weekly time points, animals were evaluated for mechanical
allodynia, thermal hyperalgesia, and gait characteristics
through digitized video analysis. Serum cytokine content was
measured after animal sacrifice, and immunohistochemistry
tested DRG tissue for mediators of inflammation and immune
activation. RESULTS: Sensory testing revealed mechanical
allodynia in the affected limb of NP-treated rats compared
with sham animals (P < 0.01) at all time points. Gait
analysis reflected functional locomotive consequences of
marked asymmetry (P = 0.048) and preference to bear weight
on the contralateral limb (duty factor imbalance, P < 0.01)
at early time points. Equivalent serum cytokine expression
occurred in both groups, confirming the local inflammatory
nature of this disease model. Immunohistochemistry of the
sectioned DRGs revealed equivalent postsurgical inflammatory
activation (interleukin 23, P = 0.47) but substantial early
immune activation in the NP-treated group (interleukin 17, P
= 0.01). CONCLUSIONS: This model of radiculopathy provides
evidence of altered gait in a model of noncompressive disc
herniation. Systemic inflammation was absent, but mechanical
allodynia, local inflammation, and autoreactive immune
activation were observed. Future work will involve
therapeutic interventions to rescue animals from the
phenotype of inflammatory radiculopathy.},
Language = {eng},
Doi = {10.1097/BRS.0b013e318197f013},
Key = {fds188646}
}
@article{fds160657,
Title = {Addison, S, R Edward Coleman, Sheng Feng, G McDaniel, and VB
Kraus. 2009. Whole body bone scintigraphy provides a measure
of total body burden of osteoarthritis for the purpose of
systemic biomarker validation. Arthritis Rheum (in
press).
},
Year = {2009},
Key = {fds160657}
}
@article{fds160658,
Title = {Griffin, TM, JL Huebner, VB Kraus, and F Guilak. 2009.
Extreme
obesity due to impaired leptin signaling in
mice does not increase knee osteoarthritis. Arthritis
Rheumatism (in press).},
Year = {2009},
Key = {fds160658}
}
@article{fds160649,
Author = {JB Catterall and D Barr and M Bolognesi and RD Zura and VB
Kraus},
Title = {Post-translational aging of proteins in osteoarthritic
cartilage and synovial fluid as measured by isomerized
aspartate.},
Journal = {Arthritis research & therapy, England},
Volume = {11},
Number = {2},
Pages = {R55},
Year = {2009},
ISSN = {1478-6362},
Keywords = {Aged • Aged, 80 and over • Aspartic Acid •
Biological Markers • Cartilage, Articular •
Glycosaminoglycans • Humans • Isomerism •
Middle Aged • Osteoarthritis, Knee • Protein
Processing, Post-Translational • Proteins •
Synovial Fluid • analysis • chemistry •
metabolism • metabolism* • pathology •
physiology*},
Abstract = {INTRODUCTION: Aging proteins undergo non-enzymatic
post-translational modification, including isomerization and
racemization. We hypothesized that cartilage with many
long-lived components could accumulate non-enzymatically
modified amino acids in the form of isomerized aspartate and
that its liberation due to osteoarthritis (OA)-related
cartilage degradation could reflect OA severity. METHODS:
Articular cartilage and synovial fluid were obtained from 14
randomly selected total knee arthroplasty cases (56 to 79
years old) and non-arthritis cartilage from 8 trauma cases
(51 to 83 years old). Paired lesional cartilage and
non-lesioned OA cartilage were graded histologically using a
modified Mankin system. Paired cartilage and synovial fluids
were assayed for isomerized aspartate, phosphate-buffered
saline/EDTA (ethylenediaminetetraacetic acid) extractable
glycosaminoglycans, and total protein. Macroscopically
normal non-lesioned OA cartilage was separated into
superficial and deep regions when cartilage thickness was at
least 3 mm (n = 6). RESULTS: Normalized to cartilage wet
weight, normal cartilage and deep non-lesioned OA cartilage
contained significantly (P < 0.05) more isomerized aspartate
than superficial non-lesioned OA cartilage and lesioned
cartilage. Synovial fluid isomerized aspartate correlated
positively (R2 = 0.53, P = 0.02) and glycosaminoglycans
correlated negatively (R2 = 0.42, P = 0.04) with
histological OA lesion severity. Neither synovial fluid
isomerized aspartate nor glycosaminoglycans nor total
protein correlated with histological scores of non-lesioned
areas. CONCLUSIONS: We show for the first time that human
cartilage and synovial fluid contain measurable quantities
of an isomerized amino acid and that synovial fluid
concentrations of isomerized aspartate reflected severity of
histological OA. Further assessment is warranted to identify
the cartilage proteins containing this modification and to
assess the functional consequences and biomarker
applications of this analyte in OA.},
Key = {fds160649}
}
@article{fds160654,
Author = {TV Stabler and SS Byers and RD Zura and VB Kraus},
Title = {Amino acid racemization reveals differential protein
turnover in osteoarthritic articular and meniscal
cartilages.},
Journal = {Arthritis research & therapy, England},
Volume = {11},
Number = {2},
Pages = {R34},
Year = {2009},
ISSN = {1478-6362},
Keywords = {Adult • Age Factors • Aged • Aged, 80 and
over • Amino Acids • Cartilage, Articular •
Chromatography, High Pressure Liquid • Dentin •
Humans • Isomerism • Menisci, Tibial • Middle
Aged • Osteoarthritis, Knee • chemistry •
metabolism • metabolism*},
Abstract = {INTRODUCTION: Certain amino acids within proteins have been
reported to change from the L form to the D form over time.
This process is known as racemization and is most likely to
occur in long-lived low-turnover tissues such as normal
cartilage. We hypothesized that diseased tissue, as found in
an osteoarthritic (OA) joint, would have increased turnover
reflected by a decrease in the racemized amino acid content.
METHODS: Using high-performance liquid chromatography
methods, we quantified the L and D forms of amino acids
reported to racemize in vivo on a biological timescale:
alanine, aspartate (Asp), asparagine (Asn), glutamate,
glutamine, isoleucine, leucine (Leu), and serine (Ser).
Furthermore, using a metabolically inactive control material
(tooth dentin) and a control material with normal metabolism
(normal articular cartilage), we developed an age adjustment
in order to make inferences about the state of protein
turnover in cartilage and meniscus. RESULTS: In the
metabolically inactive control material (n = 25, ages 13 to
80 years) and the normal metabolizing control material (n =
19, ages 17 to 83 years), only Asp + Asn (Asx), Ser, and Leu
showed a significant change (increase) in racemization with
age (P < 0.01). The age-adjusted proportions of racemized to
total amino acid (D/D+L expressed as a percentage of the
control material) for Asx, Ser, and Leu when compared with
the normal articular cartilage control were 97%, 74%, and
73% in OA meniscal cartilage and 97%, 70%, and 78% in OA
articular cartilage. We also observed lower amino acid
content in OA articular and meniscal cartilages compared
with normal articular cartilage as well as a loss of total
amino acids with age in the OA meniscal but not the OA
articular cartilage. CONCLUSIONS: These data demonstrate
comparable anabolic responses for non-lesioned OA articular
cartilage and OA meniscal cartilage but an excess of
catabolism over anabolism for the meniscal
cartilage.},
Key = {fds160654}
}
@article{fds160652,
Author = {CD Gordon and TV Stabler and VB Kraus},
Title = {Variation in osteoarthritis biomarkers from activity not
food consumption.},
Journal = {Clinica chimica acta; international journal of clinical
chemistry, Netherlands},
Volume = {398},
Number = {1-2},
Pages = {21-6},
Year = {2008},
Month = {December},
ISSN = {0009-8981},
Keywords = {Aged • Aged, 80 and over • Biological Markers
• Circadian Rhythm • Collagen Type II •
Eating • Epitopes • Extracellular Matrix Proteins
• Female • Glycoproteins • Humans •
Hyaluronic Acid • Keratan Sulfate • Knee •
Male • Middle Aged • Motor Activity •
Osteoarthritis • Transforming Growth Factor beta •
diagnosis • genetics • metabolism •
metabolism* • physiology* • radiography},
Abstract = {BACKGROUND: To optimize sampling and to understand sources
of variation in biomarkers for osteoarthritis (OA), we
evaluated variation due to activity and food consumption.
METHODS: Twenty participants, with radiographic knee OA,
provided serial serum and urine samples at 4 time points:
before arising in the morning; after 1 h of light activity;
1 h after eating breakfast; and in the evening. Five serum
(s) and 2 urinary (u) analytes were measured: hyaluronan
(sHA); cartilage oligomeric matrix protein (sCOMP); keratan
sulfate (sKS-5D4); transforming growth factor beta
(sTGF-ss1); and collagen II-related epitopes (sCPII, uCTXII,
and uC2C). Activity was monitored by an accelerometer.
RESULTS: All serum biomarkers increased and one of the
urinary biomarkers decreased after 1 h of non-exertional
activity. Food consumption following activity was associated
with a return of biomarker concentrations to baseline
levels. Accelerometers proved to be a novel way to monitor
protocol compliance and demonstrated a positive association
between the mean level of activity and sCOMP concentration.
Urinary CTXII varied the least but demonstrated both true
circadian variation (peak in the morning and nadir in the
evening) and the most robust correlation with radiographic
knee OA. CONCLUSIONS: We confirm activity related variation
in these markers. These data suggested that biomarkers also
varied due to upright posture, glomerular filtration rate
stimulated by food intake, and circadian rhythm in the case
of uCTXII.},
Key = {fds160652}
}
@article{fds160656,
Author = {DR Seifer and BD Furman and F Guilak and SA Olson and SC Brooks and VB
Kraus},
Title = {Novel synovial fluid recovery method allows for
quantification of a marker of arthritis in
mice.},
Journal = {Osteoarthritis and cartilage / OARS, Osteoarthritis Research
Society, England},
Volume = {16},
Number = {12},
Pages = {1532-8},
Year = {2008},
Month = {December},
ISSN = {1522-9653},
Keywords = {Alginates • Animals • Biological Markers •
Cartilage, Articular • Fractures, Bone •
Immunohistochemistry • Lyases • Mice •
Osteoarthritis • Pilot Projects • Synovial Fluid
• injuries • metabolism* • pharmacology
• physiology • physiopathology},
Abstract = {OBJECTIVE: We evaluated three methodologies--a calcium
sodium alginate compound (CSAC), polyacrylate beads (PABs),
and Whatman paper recovery (WPR)--for the ability to recover
synovial fluid (SF) from mouse knees in a manner that
facilitated biochemical marker analysis. METHODS: Pilot
testing of each of these recovery vehicles was conducted
using small volumes of waste human SF. CSAC emerged as the
method of choice, and was used to recover and quantify SF
from the knees of C57BL/6 mice (n=12), six of which were
given left knee articular fractures. SF concentrations of
cartilage oligomeric matrix protein (COMP) were measured by
enzyme-linked immunosorbent assay. RESULTS: The mean
concentration ratio [(COMP(left knee))/(COMP(right knee))]
was higher in the mice subjected to articular fracture when
compared to the non-fracture mice (P=0.026). The mean total
COMP ratio (taking into account the quantitative recovery of
SF) best discriminated between fracture and non-fracture
knees (P=0.004). CONCLUSIONS: Our results provide the first
direct evidence of accelerated joint tissue turnover in a
mouse model responding to acute joint injury. These data
strongly suggest that mouse SF recovery is feasible and that
biomarker analysis of collected SF samples can augment
traditional histological analyses in mouse models of
arthritis.},
Key = {fds160656}
}
@article{fds188614,
Author = {F Eckstein and RJ Buck and D Burstein and HC Charles and J Crim and M
Hudelmaier, DJ Hunter and G Hutchins and C Jackson and VB Kraus and NE
Lane, TM Link and LS Majumdar and S Mazzuca and PV Prasad and TJ
Schnitzer, MS Taljanovic and A Vaz and B Wyman and MP Le Graverand and A9001140 Study Group},
Title = {Precision of 3.0 Tesla quantitative magnetic resonance
imaging of cartilage morphology in a multicentre clinical
trial.},
Journal = {Annals of the rheumatic diseases},
Volume = {67},
Number = {12},
Pages = {1683-8},
Year = {2008},
Month = {December},
ISSN = {1468-2060},
url = {http://dx.doi.org/10.1136/ard.2007.076919},
Keywords = {Aged • Cartilage, Articular • Female •
Follow-Up Studies • Humans • Image Interpretation,
Computer-Assisted • Knee Joint • Magnetic
Resonance Imaging • Middle Aged • Osteoarthritis,
Knee • Reproducibility of Results • Technology
Assessment, Biomedical • anatomy & histology •
drug therapy • instrumentation • methods •
pathology* • standards*},
Abstract = {OBJECTIVE: Quantitative MRI (qMRI) of cartilage morphology
is a promising tool for disease-modifying osteoarthritis
drug (DMOAD) development. Recent studies at single sites
have indicated that measurements at 3.0 Tesla (T) are more
reproducible (precise) than those at 1.5 T. Precision errors
and stability in multicentre studies with imaging equipment
from various vendors have, however, not yet been evaluated.
METHODS: A total of 158 female participants (97 Kellgren and
Lawrence grade (KLG) 0, 31 KLG 2 and 30 KLG 3) were imaged
at 7 clinical centres using Siemens Magnetom Trio and GE
Signa Excite magnets. Double oblique coronal acquisitions
were obtained at baseline and at 3 months, using water
excitation spoiled gradient echo sequences (1.0x0.31x0.31
mm3 resolution). Segmentation of femorotibial cartilage
morphology was performed using proprietary software
(Chondrometrics GmbH, Ainring, Germany). RESULTS: The
precision error (root mean square coefficient of variation
(RMS CV)%) for cartilage thickness/volume measurements
ranged from 2.1%/2.4% (medial tibia) to 2.9%/3.3% (lateral
weight-bearing femoral condyle) across all participants. No
significant differences in precision errors were observed
between KLGs, imaging sites, or scanner manufacturers/types.
Mean differences between baseline and 3 months ranged from
<0.1% (non-significant) in the medial to 0.94% (p<0.01) in
the lateral femorotibial compartment, and were 0.33%
(p<0.02) for the total femorotibial subchondral bone area.
CONCLUSIONS: qMRI performed at 3.0 T provides highly
reproducible measurements of cartilage morphology in
multicentre clinical trials with equipment from different
vendors. The technology thus appears sufficiently robust to
be recommended for large-scale multicentre
trials.},
Language = {eng},
Doi = {10.1136/ard.2007.076919},
Key = {fds188614}
}
@article{fds188660,
Author = {HC Chen and SH Shah and YJ Li and TV Stabler and JM Jordan and VB
Kraus},
Title = {Inverse association of general joint hypermobility with hand
and knee osteoarthritis and serum cartilage oligomeric
matrix protein levels.},
Journal = {Arthritis and rheumatism},
Volume = {58},
Number = {12},
Pages = {3854-64},
Year = {2008},
Month = {December},
ISSN = {0004-3591},
url = {http://dx.doi.org/10.1002/art.24319},
Keywords = {Age of Onset • Biological Markers • Cohort Studies
• Extracellular Matrix Proteins • Glycoproteins
• Hand • Humans • Hyaluronic Acid •
Joint Instability • Osteoarthritis, Knee •
Phenotype • Prevalence • blood • blood*
• epidemiology* • metabolism*},
Abstract = {OBJECTIVE: Extensive joint hypermobility, lower serum
cartilage oligomeric matrix protein (COMP) levels, and
early-onset osteoarthritis (OA) are phenotypes of inherited
pseudoachondroplasia and multiple epiphyseal dysplasia.
However, few studies have evaluated the association between
articular hypermobility and primary OA. We undertook the
present study to evaluate this association and to test the
hypothesis that COMP levels are associated with
hypermobility in patients with OA and individuals without
OA. METHODS: Two separate cohorts were available for
analysis, the CARRIAGE (CARolinas Region Interaction of
Aging Genes and Environment) extended family and a subset of
the GOGO (Genetics of Generalized Osteoarthritis) sibpair
cohort. In the CARRIAGE family, we performed hand and knee
examinations and hypermobility evaluations (Beighton
criteria) and obtained sera for measurement of COMP and
hyaluronan (HA). Data on COMP and HA levels and extensive
joint radiographic and hypermobility data were also
available for the GOGO cohort. RESULTS: The prevalence of
hypermobility was 13% in the CARRIAGE family and 5% in the
GOGO cohort. In the CARRIAGE family, hypermobility was
associated with a significantly reduced prevalence of hand
(especially proximal interphalangeal joint) and knee OA and
lower mean serum COMP levels, both in the total cohort and
in non-hand-OA subgroups. These results were further
validated in the GOGO subsets without radiographic OA, in
which hypermobility was also associated with a significantly
reduced mean serum COMP level (P < 0.0001 adjusted for age).
Serum HA levels did not differ in relation to hypermobility
in either cohort. CONCLUSIONS: The present results indicate
that there is an inverse relationship between hypermobility
and hand and knee OA, and that hypermobility is associated
with lower serum COMP levels. Genetic variations of the COMP
gene may account for some subgroups of benign joint
hypermobility.},
Language = {eng},
Doi = {10.1002/art.24319},
Key = {fds188660}
}
@article{fds188661,
Author = {SA Mazzuca and MP Hellio Le Graverand and E Vignon and DJ Hunter and CG
Jackson, VB Kraus and TM Link and TJ Schnitzer and A Vaz and HC
Charles},
Title = {Performance of a non-fluoroscopically assisted substitute
for the Lyon schuss knee radiograph: quality and
reproducibility of positioning and sensitivity to joint
space narrowing in osteoarthritic knees.},
Journal = {Osteoarthritis and cartilage / OARS, Osteoarthritis Research
Society},
Volume = {16},
Number = {12},
Pages = {1555-9},
Year = {2008},
Month = {December},
ISSN = {1522-9653},
url = {http://dx.doi.org/10.1016/j.joca.2008.04.010},
Keywords = {Diagnostic Imaging • Disease Progression • Female
• Humans • Knee Joint • Middle Aged •
Obesity • Osteoarthritis, Knee • Posture •
Severity of Illness Index • Tibia • complications
• physiology • physiopathology • radiography*
• standards*},
Abstract = {OBJECTIVE: This study evaluated the longitudinal performance
of a modified Lyon schuss (LS) knee examination in the
detection of radiographic joint space narrowing (JSN) in
knees with osteoarthritis (OA). The modified LS exam entails
two to four iterative acquisitions with empirically adjusted
angulation of the X-ray beam to achieve superimposition of
the anterior and posterior margins of the medial tibial
plateau (MTP), a marker of parallel radioanatomic alignment
that the original LS exam achieves with fluoroscopically
guided beam angulation. METHODS: Seventy-four obese women
with symptomatic knee OA underwent LS and fixed-flexion (FF,
caudal 10 degrees beam angulation) X-ray exams at baseline
and 1 year later. For 47 subjects, beam angulation for both
LS exams was guided by fluoroscopy. For 27 subjects, the
modified LS exam was performed at one or both times.
Modified and original LS procedures were evaluated relative
to concurrent FF radiographs with respect to the
inter-margin distance (IMD) at the MTP midpoint (quality and
reproducibility of alignment) and sensitivity to JSN.
RESULTS: Compared to FF radiographs, modified LS radiographs
afforded a smaller mean IMD at baseline (0.89 vs 2.06 mm,
P=0.002), more reproducible IMD (mean change=0.49 vs 0.91
mm, P=0.007) and more rapid JSN (mean=0.25 vs 0.02 mm/yr,
P=0.005). These differences paralleled those observed
between original LS and FF procedures with respect to
baseline alignment (0.96 vs 1.94 mm, P<0.001),
reproducibility of alignment (0.49 vs 1.00 mm, P<0.001) and
sensitivity to JSN (0.16 vs -0.01 mm/yr, P=0.007).
CONCLUSIONS: In clinical centers where the absence of
fluoroscopy equipment precludes use of the original LS
protocol, a modified procedure employing iterative,
empirical adjustment of the beam angle to achieve parallel
radioanatomic alignment with the MTP affords a degree of
superiority over the FF protocol with respect to quality and
reproducibility of positioning and sensitivity to JSN in OA
knees similar to that of the original.},
Language = {eng},
Doi = {10.1016/j.joca.2008.04.010},
Key = {fds188661}
}
@article{fds160651,
Author = {VB Kraus and G McDaniel and TW Worrell and S Feng and TP Vail and G Varju and RE Coleman},
Title = {Association of bone scintigraphic abnormalities with knee
malalignment and pain.},
Journal = {Annals of the rheumatic diseases},
Year = {2008},
Month = {November},
ISSN = {1468-2060},
Abstract = {OBJECTIVE: We evaluated the information content of knee bone
scintigraphy, including pattern, localization and intensity
of retention relative to radiographic features of knee
osteoarthritis (rOA), knee alignment, and knee symptoms.
METHODS: A total of 308 knees (159 subjects) with
symptomatic and radiographic knee OA (rOA) of at least one
knee were assessed by late phase technetium-99m-methylene
disphosphonate bone scintigraph, fixed-flexion knee
radiograph, full limb radiograph for knee alignment, and for
self-reported knee symptom severity. Generalized linear
models were used to control for within subject correlation
of knee data. RESULTS: The compartmental localization
(medial versus lateral) and intensity of knee bone scan
retention were associated with the pattern (varus versus
valgus) (p<0.001) and severity (p=0.0008) of knee
malalignment, and localization and severity of rOA
(p<0.0001). Bone scan agent retention in the tibiofemoral,
but not patellofemoral compartment, was associated with
severity of knee symptoms (p=0.0009), and persisted after
adjusting for rOA (p=0.0012). CONCLUSION: To our knowledge,
this is the first study describing a relationship between
knee malalignment, joint symptom severity, and compartment
specific abnormalities by bone scintigraphy. This work
demonstrates that bone scintigraphy as a sensitive and
quantitative indicator of symptomatic knee OA. Used
selectively, bone scintigraphy is a dynamic imaging modality
that holds great promise as a clinical trial screening tool
and outcome measure.},
Key = {fds160651}
}
@article{fds188619,
Author = {MP Le Graverand and EP Vignon and KD Brandt and SA Mazzuca and M
Piperno, R Buck and HC Charles and DJ Hunter and CG Jackson and VB
Kraus, TM Link and TJ Schnitzer and A Vaz and B Wyman},
Title = {Head-to-head comparison of the Lyon Schuss and fixed flexion
radiographic techniques. Long-term reproducibility in normal
knees and sensitivity to change in osteoarthritic
knees.},
Journal = {Annals of the rheumatic diseases},
Volume = {67},
Number = {11},
Pages = {1562-6},
Year = {2008},
Month = {November},
ISSN = {1468-2060},
url = {http://dx.doi.org/10.1136/ard.2007.077834},
Keywords = {Adult • Aged • Arthrography • Disease
Progression • Epidemiologic Methods • Female
• Humans • Image Interpretation, Computer-Assisted
• Knee Joint • Middle Aged • Observer
Variation • Osteoarthritis, Knee • Posture •
Severity of Illness Index • anatomy & histology •
methods • pathology • radiography*},
Abstract = {OBJECTIVE: The Lyon Schuss (LS) and fixed flexion (FF) views
of the knee are superior to a conventional standing
anteroposterior view in evaluating joint space narrowing
(JSN) in osteoarthritis (OA). Both position the knee
identically but only the LS aligns the medial tibial plateau
(MTP) with the x-ray beam fluoroscopically. The present
study provides the first head-to-head comparison of the LS
and FF views. METHODS: At baseline and 12 months, 62 OA and
99 control knees were imaged twice on the same day with LS
and FF views. Minimum joint space width (mJSW) was measured
by computer and MTP alignment was assessed from the distance
between anterior and posterior margins of the MTP
(intermargin distance, IMD). Reproducibility of measurements
of mJSW and sensitivity to change were evaluated. RESULTS:
In normal knees, JSW did not vary over 12 months with either
view. In OA knees, 12-month mJSN was 0.22 (0.43) mm with the
LS view and -0.01 (0.46) mm with the FF view (p = 0.0002 and
p = 0.92, respectively). Mean IMD was only half as large in
LS as in FF views (0.9 (0.5) mm vs 1.9 (1.2) mm, p<0.0001).
CONCLUSIONS: LS and FF radiographs offer similar
reproducibility in JSW measurement. However, presumably due
to its superiority in aligning the MTP, the LS view is much
more sensitive to JSN in OA knees.},
Language = {eng},
Doi = {10.1136/ard.2007.077834},
Key = {fds188619}
}
@article{fds160650,
Author = {DJ Quintana and P Garnero and JL Huebner and N Charni-Ben Tabassi and VB
Kraus},
Title = {PIIANP and HELIXII diurnal variation.},
Journal = {Osteoarthritis and cartilage / OARS, Osteoarthritis Research
Society, England},
Volume = {16},
Number = {10},
Pages = {1192-5},
Year = {2008},
Month = {October},
ISSN = {1522-9653},
Keywords = {Adult • Aged • Aged, 80 and over • Biological
Markers • Cartilage, Articular • Circadian Rhythm
• Cohort Studies • Collagen Type II • Female
• Humans • Male • Middle Aged •
Osteoarthritis, Knee • Peptide Fragments •
Statistics as Topic • blood • metabolism •
metabolism* • pathology*},
Abstract = {OBJECTIVE: Serum levels of procollagen type IIA N-terminal
propeptide (sPIIANP) and type-II collagen helical peptide
(sHELIXII) biomarkers were evaluated for variation diurnally
and with physical activity and food in participants with
osteoarthritis (OA) of the knee. METHODS: Forty participants
with OA of at least one knee were admitted overnight to the
General Clinical Research Center for serial serum sampling.
Samples were obtained on the evening (6-8 pm) of Day 1 (T3,
n=40); prior to rising (8 am) from bed (T0, n=40); 1 h after
rising (9 am) without food consumption (T1a, n=20); 1-2 h
after rising (9-10 am) with food consumption (T1, n=40); and
additionally at noon, 4 h after rising (T2, n=20). sPIIANP
and sHELIXII were measured by enzyme-linked immunosorbent
assay. Results were analyzed using non-parametric Freidman's
test with Dunn's post-hoc multiple comparison test. RESULTS:
Normalized mean concentrations for sPIIANP and sHELIXII
increased significantly from T0 to T1 (P<0.05). CONCLUSIONS:
This is the first study to demonstrate diurnal variation of
these collagen-II biomarkers in individuals with knee OA.
These results suggest that serum sampling for these markers
should be standardized for purposes of clinical
trials.},
Key = {fds160650}
}
@article{fds188638,
Author = {U Atif and A Philip and J Aponte and EM Woldu and S Brady and VB Kraus and JM
Jordan, M Doherty and AG Wilson and RW Moskowitz and M Hochberg and R
Loeser, JB Renner and M Chiano},
Title = {Absence of association of asporin polymorphisms and
osteoarthritis susceptibility in US Caucasians.},
Journal = {Osteoarthritis and cartilage / OARS, Osteoarthritis Research
Society},
Volume = {16},
Number = {10},
Pages = {1174-7},
Year = {2008},
Month = {October},
ISSN = {1522-9653},
url = {http://dx.doi.org/10.1016/j.joca.2008.03.007},
Keywords = {Aged • Aspartic Acid • European Continental
Ancestry Group • Extracellular Matrix Proteins •
Female • Genetic Predisposition to Disease •
Genotype • Hand Joints • Humans • Knee Joint
• Male • Middle Aged • Osteoarthritis •
Pedigree • Polymorphism, Genetic • Siblings •
Statistics as Topic • United States • ethnology
• genetics • genetics* • metabolism •
physiopathology},
Abstract = {OBJECTIVE: An association between osteoarthritis (OA) and
functional polymorphisms in the aspartic acid (d) repeat of
the asporin (ASPN) gene was reported in Japanese and Han
Chinese populations. The aim of this study was to assess the
association of variants in the ASPN gene with the presence
of radiographic hand and/or knee OA in a US Caucasian
population. METHODS: Ten single nucleotide polymorphisms
(SNPs) within the ASPN gene were genotyped in 775 affected
siblings with radiographically confirmed hand and/or knee
OA, and the allelic, genotypic and haplotypic association
results were examined. RESULTS: One variant (SNP RS7033979)
showed nominal evidence of association with both hand OA
(P=0.042) and knee OA (P=0.032). Four additional SNPs showed
nominal evidence of association with knee OA only. These
associations were only observed with genotypic tests; the
corresponding allelic and haplotype tests did not
corroborate the single-point association results.
CONCLUSIONS: These data suggest that polymorphisms within
ASPN are not a major influence in susceptibility to hand or
knee OA in US Caucasians.},
Language = {eng},
Doi = {10.1016/j.joca.2008.03.007},
Key = {fds188638}
}
@article{fds160653,
Author = {HC Chen and S Shah and TV Stabler and YJ Li and VB Kraus},
Title = {Biomarkers associated with clinical phenotypes of hand
osteoarthritis in a large multigenerational family: the
CARRIAGE family study.},
Journal = {Osteoarthritis and cartilage / OARS, Osteoarthritis Research
Society, England},
Volume = {16},
Number = {9},
Pages = {1054-9},
Year = {2008},
Month = {September},
ISSN = {1522-9653},
Abstract = {OBJECTIVE: To evaluate biological markers as potential
quantitative traits of clinical osteoarthritis (OA) in a
large multigenerational family in the Carolinas of the USA
known as the CARRIAGE (CARolinas Region Interaction of
Aging, Genes and Environment) family. METHODS: During a
series of three family reunions over 6 years, we ascertained
365 family members. We performed clinical hand examinations
(n=287), and obtained sera (n=278) for seven OA-related
biomarkers [type IIA collagen N-propeptide (PIIANP), type II
procollagen carboxy-propeptide (CPII), neoepitope from
cleavage of CII (C(2)C), cartilage oligomeric matrix protein
(COMP), hyaluronan (HA), high-sensitive C-reactive protein
(hs-CRP), and glycated serum protein (GSP)]. Three hand OA
definitions were evaluated--clinical ACR (American College
of Rheumatology) and GOGO (Genetics of Generalized OA)
criteria, and any single hand joint involvement. Non-hand OA
was defined as a negative hand examination for OA but
varying prevalence of joint symptoms; the control group was
defined as having neither symptoms nor evidence for clinical
hand OA. RESULTS: Mean lnHA, lnCOMP, and lnhs-CRP were
significantly higher in the hand OA group, compared with the
non-hand OA or control group. Adjusted for age and sex, mean
lnPIIANP (a collagen II synthesis marker) was significantly
lower in the hand OA group compared with the other groups.
Among those without clinical hand OA, GSP was associated
with hand joint symptoms. CONCLUSIONS: This is the first
report, to our knowledge, showing an association of OA
biomarkers and hand OA based on physical examination alone.
Analyses using these biomarkers as quantitative traits could
reveal novel genetic loci and facilitate exploration of the
genetic susceptibility to OA.},
Key = {fds160653}
}
@article{fds87747,
Author = {JJ Pells and RA Shelby and FJ Keefe and KE Dixon and JA Blumenthal and L
Lacaille, JM Tucker and D Schmitt and DS Caldwell and VB
Kraus},
Title = {Arthritis self-efficacy and self-efficacy for resisting
eating: relationships to pain, disability, and eating
behavior in overweight and obese individuals with
osteoarthritic knee pain.},
Journal = {Pain},
Volume = {136},
Number = {3},
Pages = {340-7},
Year = {2008},
Month = {June},
ISSN = {1872-6623},
url = {http://dx.doi.org/10.1016/j.pain.2007.07.012},
Keywords = {Arthralgia • Comorbidity • Disability Evaluation
• Employment • Feeding Behavior* • Female
• Humans • Male • Middle Aged • North
Carolina • Obesity • Osteoarthritis, Knee •
Overweight • Prevalence • Prognosis • Risk
Assessment • Self Efficacy* • epidemiology •
epidemiology* • methods* • prevention & control
• statistics & numerical data},
Abstract = {This study examined arthritis self-efficacy and
self-efficacy for resisting eating as predictors of pain,
disability, and eating behaviors in overweight or obese
patients with osteoarthritis (OA) of the knee. Patients
(N=174) with a body mass index between 25 and 42 completed
measures of arthritis-related self-efficacy, weight-related
self-efficacy, pain, physical disability, psychological
disability, overeating, and demographic and medical
information. Hierarchical linear regression analyses were
conducted to examine whether arthritis self-efficacy
(efficacy for pain control, physical function, and other
symptoms) and self-efficacy for resisting eating accounted
for significant variance in pain, disability, and eating
behaviors after controlling for demographic and medical
characteristics. Analyses also tested whether the
contributions of self-efficacy were domain specific. Results
showed that self-efficacy for pain accounted for 14% (p=.01)
of the variance in pain, compared to only 3% accounted for
by self-efficacy for physical function and other symptoms.
Self-efficacy for physical function accounted for 10%
(p=.001) of the variance in physical disability, while
self-efficacy for pain and other symptoms accounted for 3%.
Self-efficacy for other (emotional) symptoms and resisting
eating accounted for 21% (p<.05) of the variance in
psychological disability, while self-efficacy for pain
control and physical function were not significant
predictors. Self-efficacy for resisting eating accounted for
28% (p=.001) of the variance in eating behaviors. Findings
indicate that self-efficacy is important in understanding
pain and behavioral adjustment in overweight or obese OA
patients. Moreover, the contributions of self-efficacy were
domain specific. Interventions targeting both arthritis
self-efficacy and self-efficacy for resisting eating may be
helpful in this population.},
Language = {eng},
Doi = {10.1016/j.pain.2007.07.012},
Key = {fds87747}
}
@article{fds160655,
Author = {BD Ward and BD Furman and JL Huebner and VB Kraus and F Guilak and SA
Olson},
Title = {Absence of posttraumatic arthritis following intraarticular
fracture in the MRL/MpJ mouse.},
Journal = {Arthritis and rheumatism, United States},
Volume = {58},
Number = {3},
Pages = {744-53},
Year = {2008},
Month = {March},
ISSN = {0004-3591},
Keywords = {Animals • Arthritis • Biological Markers •
Bone Regeneration • Cartilage • Disease Models,
Animal • Fractures, Bone • Interleukin-10 •
Interleukin-1alpha • Interleukin-4 • Joints •
Male • Mice • Mice, Inbred C57BL • Mice,
Inbred Strains • blood • complications* •
etiology* • genetics • injuries* • pathology
• physiology • physiopathology},
Abstract = {OBJECTIVE: Posttraumatic arthritis is a frequent long-term
complication of intraarticular fractures. A model of a
closed intraarticular fracture in C57BL/6 mice that
progresses to posttraumatic arthritis has been developed.
The MRL/MpJ mouse has shown unique regenerative abilities in
response to injury. The objective of this study was to
determine if the MRL/MpJ mouse is protected from
posttraumatic arthritis after intraarticular fractures.
METHODS: Intraarticular fractures were created in MRL/MpJ
mice and C57BL/6 control mice (n = 16 each). Limbs were
analyzed for posttraumatic arthritis 4 and 8 weeks after
fracture using microfocal computed tomography bone
morphology, subchondral bone thickness evaluation, and
histologic evaluation of cartilage degeneration. Serum
cytokines and biomarkers were measured after the mice were
killed. RESULTS: Intraarticular fractures were successfully
created in all 32 mice. In the experimental fractured limbs,
C57BL/6 mice had a decrease in bone density, increased
subchondral bone thickness, and increased cartilage
degeneration compared with normal contralateral control
limbs. In the MRL/MpJ mice, no differences in bone density,
subchondral bone thickness, or histologic grading of
cartilage degeneration were seen between fractured and
contralateral control limbs. Cytokine analysis showed lower
systemic levels of the proinflammatory cytokine
interleukin-1alpha (IL-1alpha) and higher levels of the
antiinflammatory cytokines IL-4 and IL-10 in the MRL/MpJ
mice. CONCLUSION: This study shows that the MRL/MpJ mouse is
relatively protected from posttraumatic arthritis after
intraarticular fracture. Further investigation into the
mechanism involved in this response will hopefully provide
new insight into the pathogenesis, prevention, and treatment
of posttraumatic arthritis after intraarticular
fracture.},
Key = {fds160655}
}
@article{fds87738,
Author = {AL Elliott and VB Kraus and F Fang and JB Renner and TA Schwartz and A
Salazar, T Huguenin and MC Hochberg and CG Helmick and JM
Jordan},
Title = {Joint-specific hand symptoms and self-reported and
performance-based functional status in African Americans and
Caucasians: The Johnston County Osteoarthritis
Project.},
Journal = {Annals of the rheumatic diseases},
Volume = {66},
Number = {12},
Pages = {1622-6},
Year = {2007},
Month = {December},
ISSN = {1468-2060},
url = {http://dx.doi.org/10.1136/ard.2006.057422},
Keywords = {Activities of Daily Living* • Adult • African
Americans • Age Factors • Aged • Aged, 80 and
over • Analysis of Variance • Arthrography •
European Continental Ancestry Group • Female •
Hand Joints • Hip Joint • Humans • Knee Joint
• Linear Models • Male • Middle Aged •
Osteoarthritis • Osteoarthritis, Hip •
Osteoarthritis, Knee • Range of Motion, Articular
• Sex Factors • ethnology • physiopathology
• physiopathology* • radiography},
Abstract = {OBJECTIVE: To assess associations between joint-specific
hand symptoms and self-reported and performance-based
functional status. METHODS: Participants were from the
population-based Johnston County Osteoarthritis Project.
Symptoms in the distal interphalangeal (DIP), proximal
interphalangeal (PIP), first carpometacarpal (CMC), and
metacarpophalangeal (MCP) joints were assessed on a 30-joint
diagram of both hands. Self-reported function was assessed
by Health Assessment Questionnaire (HAQ) and
performance-based function by timed repeated chair stands
and 8-foot walk time. Separate multiple logistic regression
models examined associations between symptoms in specific
hand joint groups, symptoms in >/=2 hand joint groups and
number of symptomatic hand joints, and functional status
measures, controlling for age, race/ethnicity, sex, body
mass index, radiographic knee and hip OA, knee and hip
symptoms and depressive symptoms. RESULTS: Those with
symptomatic hand joint groups were more likely than those
without these complaints to report more difficulty and
require longer times for performance measures. Those with 2
or more symptomatic hand joint groups were more likely to
have higher HAQ scores (OR = 1.97 (1.53 to 2.53)) and
require more time to complete 5 chair stands (OR = 1.98
(1.23 to 3.18)) and the 8 foot walk test (OR = 1.49 (1.12 to
1.99)). CONCLUSIONS: Joint-specific hand symptoms are
associated with difficulty performing upper- or
lower-extremity tasks, independent of knee and hip OA and
symptoms, suggesting that studies examining functional
status in OA should not ignore symptomatic joints beyond the
joint site of interest, even when functional measures appear
to be specific for the joint site under study.},
Language = {eng},
Doi = {10.1136/ard.2006.057422},
Key = {fds87738}
}
@article{fds87741,
Author = {MF Shamji and H Betre and VB Kraus and J Chen and A Chilkoti and R Pichika and K Masuda and LA Setton},
Title = {Development and characterization of a fusion protein between
thermally responsive elastin-like polypeptide and
interleukin-1 receptor antagonist: sustained release of a
local antiinflammatory therapeutic.},
Journal = {Arthritis and rheumatism},
Volume = {56},
Number = {11},
Pages = {3650-61},
Year = {2007},
Month = {November},
ISSN = {0004-3591},
url = {http://dx.doi.org/10.1002/art.22952},
Keywords = {Animals • Anti-Inflammatory Agents • Cell Division
• Chondrocytes • Drug Delivery Systems • Drug
Design • Elastin • Humans • Interleukin 1
Receptor Antagonist Protein • Intervertebral Disc
• Lymphocytes • Mice • Mice, Inbred C57BL
• Peptides • Receptors, Interleukin-1 •
Recombinant Fusion Proteins • Temperature • Thymus
Gland • U937 Cells • cytology • drug effects
• genetics • genetics* • immunology •
metabolism • methods • pharmacokinetics*},
Abstract = {OBJECTIVE: Interleukin-1 receptor antagonist (IL-1Ra) has
been evaluated for the intraarticular treatment of
osteoarthritis. Such administration of proteins may have
limited utility because of their rapid clearance and short
half-life in the joint. The fusion of a drug to elastin-like
polypeptides (ELPs) promotes the formation of aggregating
particles that form a "drug depot" at physiologic
temperatures, a phenomenon intended to prolong the presence
of the drug. The purpose of this study was to develop an
injectable drug depot composed of IL-1Ra and ELP domains and
to evaluate the properties and bioactivity of the
recombinant ELP-IL-1Ra fusion protein. METHODS: Fusion
proteins between IL-1Ra and 2 distinct sequences and
molecular weights of ELP were overexpressed in Escherichia
coli. Environmental sensitivity was demonstrated by
turbidity and dynamic light scattering as a function of
temperature. IL-1Ra domain activity was evaluated by surface
plasmon resonance, and in vitro antagonism of IL-1-mediated
lymphocyte and thymocyte proliferation, as well as
IL-1-induced tumor necrosis factor alpha (TNFalpha)
expression and matrix metalloproteinase 3 (MMP-3) and
ADAMTS-4 messenger RNA expression in human intervertebral
disc fibrochondrocytes. IL-1Ra immunoreactivity was assessed
before and after proteolytic degradation of the ELP partner.
RESULTS: Both fusion proteins underwent supramolecular
aggregation at subphysiologic temperatures and slowly
resolubilized at 37 degrees C. Interaction with IL-1
receptor was slower in association but equivalent in
dissociation as compared with the commercial antagonist.
Anti-IL-1 activity was demonstrated by inhibition of
lymphocyte and thymocyte proliferation and by decreased
TNFalpha expression and ADAMTS-4 and MMP-3 transcription by
fibrochondrocytes. ELP domain proteolysis liberated a
peptide of comparable size and immunoreactivity as the
commercial IL-1Ra. This peptide was more bioactive against
lymphocyte proliferation, nearly equivalent to the
commercial antagonist. CONCLUSIONS: The ELP-IL-1Ra fusion
protein proved to retain the characteristic ELP inverse
phase-transitioning behavior as well as the bioactivity of
the IL-1Ra domain. This technology represents a novel drug
carrier designed to prolong the presence of bioactive
peptides following intraarticular delivery.},
Language = {eng},
Doi = {10.1002/art.22952},
Key = {fds87741}
}
@article{fds87743,
Author = {HC Charles and VB Kraus and M Ainslie and MP Hellio Le
Graverand-Gastineau},
Title = {Optimization of the fixed-flexion knee radiograph.},
Journal = {Osteoarthritis and cartilage / OARS, Osteoarthritis Research
Society},
Volume = {15},
Number = {11},
Pages = {1221-4},
Year = {2007},
Month = {November},
ISSN = {1063-4584},
url = {http://dx.doi.org/10.1016/j.joca.2007.05.012},
Keywords = {Humans • Knee Joint • Osteoarthritis, Knee •
Reproducibility of Results • radiography*},
Abstract = {OBJECTIVE: To develop a user-friendly method of achieving
optimal radiographs for measurement of joint space width of
the knee with minimal radiation exposure. In order to
accomplish this the X-ray technologist must (1) be able to
identify the anterior and posterior rims of the tibial
plateau at a variety of X-ray head angles and (2) be able to
choose the direction to adjust the head angle to get a
better view based on the criteria for acceptable
radiographs. METHODS: We have developed a training manual
and materials to instruct investigators and radiology
technologists in a method that uses a commercially available
Plexiglas positioning frame (Synaflexer) and standard X-ray
equipment to achieve optimal X-rays with regard to tibial
plateau alignment of the knee. This should be accomplished
with four or fewer radiographs. RESULTS: Optimized
radiographs for joint space width measurements are achieved
without the need for fluoroscopy or foot maps. CONCLUSIONS:
This method is readily understood and instituted by
radiology technologists in the field.},
Language = {eng},
Doi = {10.1016/j.joca.2007.05.012},
Key = {fds87743}
}
@article{fds87742,
Author = {VB Kraus and TV Stabler and SY Kong and G Varju and G
McDaniel},
Title = {Measurement of synovial fluid volume using
urea.},
Journal = {Osteoarthritis and cartilage / OARS, Osteoarthritis Research
Society},
Volume = {15},
Number = {10},
Pages = {1217-20},
Year = {2007},
Month = {October},
ISSN = {1063-4584},
url = {http://dx.doi.org/10.1016/j.joca.2007.03.017},
Keywords = {Humans • Knee Joint • Osteoarthritis, Knee •
Pain Measurement • Statistics as Topic • Synovial
Fluid • Urea • chemistry* • diagnostic use*
• metabolism • metabolism*},
Abstract = {OBJECTIVE: To examine the utility of using urea
concentrations for determining Synovial Fluid (SF) joint
volume in effused and non-effused joints. METHODS: Knee
joint SF was aspirated from 159 human study participants
with symptomatic osteoarthritis of at least one knee either
directly (165 knees) or by lavage (110 knees). Serum was
obtained immediately prior to SF aspiration. Participants
were asked to rate individual knee pain, aching or
stiffness. SF and serum urea levels were determined using a
specific enzymatic method run on an automated CMA600
analyzer. Cell counts were performed on direct SF aspirates
when volume permitted. The formula for calculating SF joint
volume was as follows: V(j)=C(D)(V(I))/(C-C(D)) with
V(j)=volume of SF in entire joint, C(D)=concentration of
urea in diluted (lavage) SF, V(I)=volume of saline injected
into joint, and C=concentration of urea in undiluted (neat)
SF derived below where C=0.897(C(S)) and C(s)=concentration
of urea in serum. RESULTS: There was an excellent
correlation (r(2)=0.8588) between SF and serum urea in the
direct aspirates with a ratio of 0.897 (SF/serum). Neither
urea levels nor the SF/serum ratio showed any correlation
with Kellgren Lawrence (KL) grade, or cell count. While urea
levels increased with age there was no change in the ratio.
Intraarticular SF volumes calculated for the lavaged knees
ranged from 0.555 to 71.71ml with a median volume of
3.048ml. There was no correlation of SF volume to KL grade
but there was a positive correlation (P=0.001) between SF
volume and self-reported individual knee pain. CONCLUSIONS:
Our urea results for direct aspirates indicate an
equilibrium state between serum and SF with regard to the
water fraction. This equilibrium exists regardless of
disease status (KL grade), inflammation (cell count), or
age, making it possible to calculate intraarticular volume
of lavaged joints based upon this urea method. Most of the
joint volumes we calculated fell within the previously
reported range for normal knees of 0.5-4.0ml. The positive
correlation between SF volume and knee symptoms reinforces
the clinical utility of this method for quantifying SF
volume.},
Language = {eng},
Doi = {10.1016/j.joca.2007.03.017},
Key = {fds87742}
}
@article{fds87739,
Author = {VB Kraus and TV Stabler and G Luta and JB Renner and AD Dragomir and JM
Jordan},
Title = {Interpretation of serum C-reactive protein (CRP) levels for
cardiovascular disease risk is complicated by race,
pulmonary disease, body mass index, gender, and
osteoarthritis.},
Journal = {Osteoarthritis and cartilage / OARS, Osteoarthritis Research
Society},
Volume = {15},
Number = {8},
Pages = {966-71},
Year = {2007},
Month = {August},
ISSN = {1063-4584},
url = {http://dx.doi.org/10.1016/j.joca.2007.02.014},
Keywords = {African Americans • Body Mass Index • C-Reactive
Protein • Cardiovascular Diseases • Comorbidity
• European Continental Ancestry Group • Female
• Humans • Lung Diseases • Male • Middle
Aged • Obesity • Osteoarthritis • Prevalence
• Risk Factors • Sex Distribution • blood
• ethnology • ethnology* • metabolism* •
statistics & numerical data*},
Abstract = {OBJECTIVE: High-sensitivity C-reactive protein (hsCRP) in
serum is used as a marker of risk for cardiovascular disease
(CVD); however CRP is a non-specific acute phase reactant.
We evaluated the association between hsCRP concentrations
and the most common form of arthritis, osteoarthritis (OA),
and assessed the applicability of hsCRP for CVD risk
prediction. METHODS: Participants (n=662) were selected from
the population-based Johnston County Osteoarthritis Project,
using stratified simple random sampling to achieve balance
according to radiographic knee OA status, ethnic group,
gender, and age group. The presence and severity of knee and
hip OA were determined radiographically. CVD risk was
estimated by hsCRP concentration and independently with the
Framingham risk algorithm. RESULTS: Serum natural
log-transformed hsCRP (ln hsCRP) was higher in
African-Americans (P<0.0001) and women (P<0.0001), was
higher in participants who had chronic pulmonary disease
(P=0.01), hypertension (P<0.0001), or used pain medications
(P=0.004), and correlated with body mass index (BMI)
(r=0.40, P<0.0001) and waist circumference (r=0.33,
P<0.0001), but not with age, CVD, or current smoking. Ln
hsCRP was strongly positively associated with all
definitions of radiographic OA (rOA; P<0.0001), but this
association was not independent of BMI. Although 183
participants reported no CVD and were classified as low risk
by the Framingham CVD score, 61% of them were classified as
moderate or high risk for CVD using hsCRP; this proportion
designated high risk for CVD on the basis of hsCRP consisted
primarily of women (P<0.05) and individuals with OA
(P<0.01). CONCLUSIONS: The pathogenic significance of hsCRP
elevations in this subgroup is unclear. Serum hsCRP for
predicting risk of CVD is confounded by obesity, ethnicity,
gender and comorbidities.},
Language = {eng},
Doi = {10.1016/j.joca.2007.02.014},
Key = {fds87739}
}
@article{fds87748,
Author = {KD Allen and RF DeVellis and JB Renner and VB Kraus and JM
Jordan},
Title = {Validity and factor structure of the AUSCAN Osteoarthritis
Hand Index in a community-based sample.},
Journal = {Osteoarthritis and cartilage / OARS, Osteoarthritis Research
Society},
Volume = {15},
Number = {7},
Pages = {830-6},
Year = {2007},
Month = {July},
ISSN = {1063-4584},
url = {http://dx.doi.org/10.1016/j.joca.2007.01.012},
Keywords = {Activities of Daily Living • Cross-Sectional Studies
• Disability Evaluation • Female • Hand
• Hand Strength • Humans • Male • Middle
Aged • Osteoarthritis • Pain Measurement •
Questionnaires • Rheumatology • Severity of
Illness Index • methods* • physiology* •
physiopathology* • radiography •
standards},
Abstract = {OBJECTIVE: The AUStralian CANadian Osteoarthritis Hand Index
(AUSCAN) is a self-report assessment of hand pain,
stiffness, and function. Prior studies have examined its
validity in small clinical samples and family-based samples.
This study examined measurement properties of the AUSCAN in
a large, community-based sample, extending knowledge about
the scale's generalizability. METHODS: Participants (N=1730,
mean age=61 years, 65% female, 30% African American) were
enrolled in the Johnston County Osteoarthritis Project. We
examined the internal consistency, construct validity, and
factor structure of the AUSCAN among the total sample, as
well as in subgroups according to gender, race, presence of
hand pain, and presence of radiographic hand osteoarthritis
(OA). RESULTS: Internal consistency was high for the total
scale and subscales among the full study sample and all
subgroups (Cronbach's alphas=0.89-0.96). Construct validity
was also supported, as grip and pinch strength were more
strongly correlated with the AUSCAN function subscale than
with the pain and stiffness subscales. Factor analysis
showed that for the full sample and most subgroups, all pain
items loaded on one factor (standardized regression
coefficients 0.59-0.81) and all function items loaded on
another (standardized regression coefficients 0.61-0.78),
supporting the intended subscale structure of the scale.
However, for African Americans, a different factor pattern
emerged, with three function items loading on a factor with
the pain items. CONCLUSIONS: Results support the validity of
the AUSCAN in a general sample of adults, as well as across
demographic and clinical subgroups, although the subscale
structures differed slightly by race.},
Language = {eng},
Doi = {10.1016/j.joca.2007.01.012},
Key = {fds87748}
}
@article{fds87721,
Author = {KM Huffman, JR Bowers and Z Dailiana and JL Huebner, JR Urbaniak and VB Kraus},
Title = {Synovial fluid metabolites in osteonecrosis.},
Journal = {Rheumatology (Oxford, England), England},
Volume = {46},
Number = {3},
Pages = {523-8},
Year = {2007},
Month = {March},
ISSN = {1462-0324},
Keywords = {Animals • Biological Markers • Bone
Transplantation • Combined Modality Therapy •
Disease Models, Animal • Dogs • Femur Head
Necrosis • Glucose • Lactic Acid • Synovial
Fluid • Vascular Endothelial Growth Factor A •
metabolism • metabolism* • pathology •
therapeutic use • therapy},
Abstract = {OBJECTIVES: Osteonecrosis of the femoral head results from
interruption of the vascular supply and eventual death of
the cellular portion of bone. Effective methods of
monitoring response to treatment are needed. Our aim was to
evaluate synovial fluid metabolites, glucose and lactate, as
biomarkers in a canine model of osteonecrosis. METHODS:
Osteonecrosis was cryosurgically induced in the right
femoral head while the left hip served as control (n = 31).
Animals either underwent no further intervention (n = 10),
vascular endothelial growth factor (VEGF) injections (n =
4), placement of a vascularized bone graft (n = 6), a
combination of VEGF microinjection and vascularized graft
placement (n = 5), or treatment with daily oral alendronate
(n = 6). After 12 weeks, synovial fluid from each hip joint
was obtained for glucose and lactate concentrations.
RESULTS: Joints with surgically induced osteonecrosis
demonstrated decreased synovial fluid concentrations of
glucose (P < 0.05) and elevated concentrations of lactate (P
< 0.05) relative to contralateral control hips. When animals
were treated with VEGF, the vascularized graft placement, or
vascularized graft and VEGF, there were no differences in
the synovial fluid concentrations of these metabolites
between cryoablated and control hips. In contrast,
alendronate did not normalize the concentration of these
synovial fluid metabolites in the cryoablated hips.
CONCLUSIONS: Osteonecrosis of the femoral head is associated
with alterations in synovial fluid glucose and lactate,
reflecting anaerobic metabolism. These metabolites may serve
as useful tools for monitoring response to revascularization
therapies.},
Key = {fds87721}
}
@article{fds87744,
Author = {JL Huebner and DR Seifer and VB Kraus},
Title = {A longitudinal analysis of serum cytokines in the Hartley
guinea pig model of osteoarthritis.},
Journal = {Osteoarthritis and cartilage / OARS, Osteoarthritis Research
Society},
Volume = {15},
Number = {3},
Pages = {354-6},
Year = {2007},
Month = {March},
ISSN = {1063-4584},
url = {http://dx.doi.org/10.1016/j.joca.2006.10.014},
Keywords = {Animals • Biological Markers • Cytokines •
Disease Models, Animal • Guinea Pigs •
Osteoarthritis • blood • blood* •
pathology},
Abstract = {OBJECTIVE: To evaluate chosen serum cytokines and their
association with osteoarthritis (OA) in the guinea pig.
METHODS: The levels of 18 cytokines were measured in Hartley
guinea pig serum at time points ranging from 3 weeks to 18
months of age. These levels were then tested for any
correlation with total histology, and a comprehensive
evaluation of these statistics was conducted using data
previously collected from OA-resistant Strain 13 guinea
pigs. RESULTS: After all cytokines demonstrating a
significant association with weight or age were excluded,
IL-6 (p=0.016) and G-CSF (p=0.024) were found to correlate
positively with total histological score. Models involving
each of these cytokines paired independently with weight
explained 43-44% of the variance in total histology.
CONCLUSIONS: Only the age and weight-independent
associations of IL-6 and G-CSF with histological OA were
significant under the conditions imposed by the Holm
step-down adjustment for multiple comparisons. Though the
observed changes of these cytokine levels may be due to a
correlation with age, it is highly unlikely given the
significant difference between Hartley and Strain 13
age-matched cohorts.},
Language = {eng},
Doi = {10.1016/j.joca.2006.10.014},
Key = {fds87744}
}
@article{fds87745,
Author = {SO Keeling and R Landewe and D van der Heijde and J Bathon and M Boers and P Garnero and P Geusens and H El-Gabalawy and RD Inman and VB Kraus and TK
Kvien, PJ Mease and M Ostergaard and C Ritchlin and SW Syversen and WP
Maksymowych},
Title = {Testing of the preliminary OMERACT validation criteria for a
biomarker to be regarded as reflecting structural damage
endpoints in rheumatoid arthritis clinical trials: the
example of C-reactive protein.},
Journal = {The Journal of rheumatology, Canada},
Volume = {34},
Number = {3},
Pages = {623-33},
Year = {2007},
Month = {March},
ISSN = {0315-162X},
Keywords = {Arthritis, Rheumatoid • Biological Markers •
C-Reactive Protein • Consensus* • Delphi Technique
• Humans • Outcome Assessment (Health Care) •
Predictive Value of Tests • analysis • analysis*
• blood* • pathology • standards*},
Abstract = {OBJECTIVE: A list of 14 criteria for guiding the validation
of a soluble biomarker as reflecting structural damage
endpoints in rheumatoid arthritis (RA) clinical trials was
drafted by an international working group after a Delphi
consensus exercise. C-reactive protein (CRP), a soluble
biomarker extensively studied in RA, was then used to test
these criteria. Our objectives were: (1) To assess the
strength of evidence in support of CRP as a soluble
biomarker reflecting structural damage in RA according to
the draft validation criteria. (2) To assess the strength of
recommendation for inclusion of individual criteria in the
draft set. METHODS: A systematic literature review was
conducted to elicit evidence in support of each specific
criterion composing the 14-criteria draft set. A summary of
the key literature findings per criterion was presented to
both the working group and to participants in a special
interest soluble biomarker group at OMERACT 8. Participants
at OMERACT 8 were asked to rate the strength of evidence and
the strength of the recommendation in support of each
individual criterion on a 0-10 numerical rating scale.
Working group members not present at OMERACT voted by a
Web-based survey. RESULTS: Minimal data were extracted from
the literature pertaining to those criteria listed under the
category of truth. Ratings for strength of evidence were
moderate to low (< 7) for CRP as a biomarker reflecting
structural damage in RA; this was true for all criteria
except those listed under the category of feasibility and 2
listed under the category of discrimination pertaining to
assay reproducibility and evidence regarding sources of
variability. Ratings for strength of recommendation for
inclusion of each of the 14 criteria in the draft set were
high (> 7) except for those criteria listed under the
category of truth. CONCLUSION: The draft criteria serve as a
useful template in the evaluation of the strength of
evidence in support of a particular soluble biomarker as
reflecting structural damage in RA.},
Key = {fds87745}
}
@article{fds188622,
Author = {WP Maksymowych and R Landewe and M Boers and P Garnero and P Geusens and H
El-Gabalawy, D Heinegard and VB Kraus and V Krause and S Lohmander and J
Matyas, T Saxne and D van der Heijde},
Title = {Development of draft validation criteria for a soluble
biomarker to be regarded as a valid biomarker reflecting
structural damage endpoints in rheumatoid arthritis and
spondyloarthritis clinical trials.},
Journal = {The Journal of rheumatology},
Volume = {34},
Number = {3},
Pages = {634-40},
Year = {2007},
Month = {March},
ISSN = {0315-162X},
Keywords = {Arthritis, Rheumatoid • Biological Markers* •
Consensus* • Delphi Technique • Humans •
Outcome Assessment (Health Care) • Predictive Value of
Tests • Reproducibility of Results •
Spondylarthritis • Treatment Outcome • blood
• pathology* • standards*},
Abstract = {OBJECTIVE: Recent work has shown that several soluble
biomarkers, detectable in peripheral blood, synovial fluid,
and/or urine, reflect remodeling of joint tissues and may
therefore constitute outcome measures that reflect joint
damage. Consequently, it is now desirable to begin the
process of developing criteria for validation of a soluble
biomarker as an outcome measure reflecting structural damage
progression in trials of disease-modifying therapies for
rheumatoid arthritis (RA) and spondyloarthritis (SpA). Our
objective was to develop validation criteria for a soluble
biomarker to be regarded as a valid biomarker reflecting
radiological endpoints in RA and SpA clinical trials.
METHODS: A special interest group was established comprising
investigators with expertise in soluble biomarker assay
development as well as in outcomes research. This project
was initiated by means of a Delphi consensus exercise. A
list of draft criteria was first generated following a
review of a US National Institutes of Health (NIH) 2000
white paper (available at: http://www.niams.nih.gov/ne/oi/
oabiomarwhipap.htm) that focused on biomarkers in OA, and
these were organized under subject headings relevant to the
OMERACT filter: truth, discrimination, and feasibility.
Additional criteria were solicited from the working group.
This was followed by 3 rounds of voting. RESULTS: A list of
31 criteria was generated prior to voting. The first 2
rounds of voting resulted in cumulative agreement that 19
criteria be retained and 4 discarded, while discrepancies
were recorded for 8 criteria. In the third round of voting,
cumulative agreement was achieved to retain 5 of the 8
discrepant criteria, so that the final list included 24
criteria. CONCLUSIONS: A draft set of criteria for
validation of a soluble biomarker to be regarded as
reflecting radiological damage endpoints in clinical trials
has been proposed on the basis of consensus.},
Language = {eng},
Key = {fds188622}
}
@article{fds87740,
Author = {VB Kraus and JM Jordan and M Doherty and AG Wilson and R Moskowitz and M
Hochberg, R Loeser and M Hooper and JB Renner and MM Crane and P Hastie and S Sundseth and U Atif},
Title = {The Genetics of Generalized Osteoarthritis (GOGO) study:
study design and evaluation of osteoarthritis
phenotypes.},
Journal = {Osteoarthritis and cartilage / OARS, Osteoarthritis Research
Society},
Volume = {15},
Number = {2},
Pages = {120-7},
Year = {2007},
Month = {February},
ISSN = {1063-4584},
url = {http://dx.doi.org/10.1016/j.joca.2006.10.002},
Keywords = {Adult • Aged • Aged, 80 and over • Biomedical
Research • Female • Humans • Male •
Middle Aged • Osteoarthritis • Pedigree •
Phenotype • Risk Factors • diagnosis •
genetics*},
Abstract = {OBJECTIVE: The primary goal of the Genetics of Generalized
Osteoarthritis (GOGO) study is to identify chromosomal
regions associated with increased susceptibility to
generalized osteoarthritis (OA). Here we describe the study
design and phenotype of the 2728 participants from the 1145
families recruited for this study. METHODS: GOGO is an
investigator-initiated collaboration involving seven
clinical academic sites and sponsored by GlaxoSmithKline.
Family ascertainment was carried out between 1999 and 2002.
A qualifying family required self-reported Caucasian
ethnicity and at least two affected siblings with clinical
hand OA. We hypothesized that this clinical phenotype would
facilitate identification of participants with multijoint
radiographic OA (rOA) in and beyond the hand. The "gold
standard" case definition, however, was based on rOA
(Kellgren-Lawrence grade > or =2) involving > or =3 hand
joints distributed bilaterally and including at least one
distal interphalangeal joint, with two of the three involved
joints within a joint group (distal interphalangeal,
proximal interphalangeal, or carpometacarpal). Radiographs
of hips, knees and spine were also obtained. Additional
siblings and living parents from qualifying families, both
affected and unaffected, were invited to participate.
RESULTS: A total of 2706 participants had complete clinical
and radiological examination data. Of these, 2569
participants met clinical examination criteria for affected
status; while 1963 (73%) participants met the prespecified
radiographic criteria for affected status. This corresponded
to a total of 707 families with at least two affected
siblings that met the hand rOA criteria. Of those
individuals with rOA of the hand, the frequency of rOA at
other sites was highest for the knee (51%) and spine (54%),
and less common for the hip (25%). Concordance rates among
hand affected siblings were greatest for spine (36%)
followed by knee (31%) and hip (9%); a total of 53% of the
affected sib pairs were concordant for specific patterns of
generalized rOA involving the hand and large joints (knees,
hips or spine). CONCLUSIONS: GOGO represents a large
multicenter collection of families with multiple joint OA
that have been characterized both clinically and
radiographically. The GOGO study will employ a comprehensive
strategy for genetic screening based upon both qualitative
and quantitative radiographic trait analyses, circulating
biomarkers in a quantitative trait-based analysis, fine
mapping, and candidate gene analysis. This sample should
provide sufficient power to detect linkage to OA associated
genes.},
Language = {eng},
Doi = {10.1016/j.joca.2006.10.002},
Key = {fds87740}
}
@article{fds188626,
Author = {VB Kraus and JM Jordan},
Title = {Serum C-Reactive Protein (CRP), Target for Therapy or
Trouble?},
Journal = {Biomarker insights},
Volume = {1},
Pages = {77-80},
Year = {2007},
ISSN = {1177-2719},
Abstract = {High sensitivity serum C-reactive protein (hs-CRP) has come
into clinical use as a marker of risk for cardiovascular
disease (CVD). In addition to a role as a marker of disease,
CRP has also been implicated in the pathogenesis of CVD.
Specific small-molecule inhibitors of CRP have recently been
developed with the intent of mitigating cardiac damage
during acute myocardial infarction. However, the use of CRP,
both as a risk marker and a disease target are controversial
for several reasons. Serum hs-CRP concentrations can be
elevated on the basis of genetics, female gender, and
non-Caucasian ethnicity. It is not clear, in these contexts,
that elevations of hs-CRP have any pathological
significance. As a non-specific indicator of inflammation,
CRP is also not a specific indicator of a single disease
state such as cardiovascular disease but elevated
concentrations can be seen in association with other
comorbidities including obesity and pulmonary disease. In
sharp contrast to the proposed inhibition of CRP for
cardiovascular disease treatment, the infusion of CRP has
been shown to have profound therapeutic benefits for
autoimmune disease and septic shock. The balance between the
risks and benefits of these competing views of the role of
CRP in disease and disease therapy is reminiscent of the
ongoing controversy regarding the use of non-steroidal
anti-inflammatory drugs (NSAIDs) for musculoskeletal disease
and their cardiovascular side effects. Soon, NSAIDs may not
be the only agents about which Rheumatologists and
Cardiologists may spar.},
Language = {eng},
Key = {fds188626}
}
@article{fds188642,
Author = {JD Birmingham and V Vilim and VB Kraus},
Title = {Collagen biomarkers for arthritis applications.},
Journal = {Biomarker insights},
Volume = {1},
Pages = {61-76},
Year = {2007},
ISSN = {1177-2719},
Language = {eng},
Key = {fds188642}
}
@article{fds87727,
Author = {KD Allen and JM Jordan and JB Renner and VB Kraus},
Title = {Relationship of global assessment of change to AUSCAN and
pinch and grip strength among individuals with hand
osteoarthritis.},
Journal = {Osteoarthritis and cartilage / OARS, Osteoarthritis Research
Society, England},
Volume = {14},
Number = {12},
Pages = {1281-7},
Year = {2006},
Month = {December},
ISSN = {1063-4584},
Keywords = {Aged • Disease Progression • Female •
Follow-Up Studies • Hand Joints • Hand Strength*
• Humans • Male • Middle Aged • Muscle
Strength • Osteoarthritis • Reproducibility of
Results • Severity of Illness Index* • diagnosis*
• physiopathology • physiopathology*},
Abstract = {OBJECTIVE: This study assessed the utility and construct
validity of a new patient global assessment of symptom
change for hand osteoarthritis (OA) by examining its
associations with change over time in grip strength, pinch
strength, and AUStralian CANadian Osteoarthritis Hand Index
(AUSCAN). METHODS: Participants (N=531, 80% female, mean
age=68) were part of a study on the Genetics of Generalized
Osteoarthritis (GOGO) and completed two assessments (average
4 years apart). At the second assessment, participants
described change in their right and left hand pain, aching,
and stiffness on a 15-point scale with descriptors ranging
from "Great deal worse" to "Great deal better". Linear
regression models examined associations of global change
scores with changes in hand strength and AUSCAN, controlling
for age, gender, number of hand joints with OA, and time
between assessments. RESULTS: Both right and left hand
global assessment of change scores were significantly
associated with change in AUSCAN, grip strength, and right
hand pinch strength (P<0.05), and approached significance
for left hand pinch strength (P=0.06). The strongest
associations were between global change scores and AUSCAN
change (right hand: beta=0.29, P<0.001; left hand:
beta=0.27, P<0.001). Associations of change scores with grip
and pinch strength were stronger among participants with
greater radiographic OA severity at baseline. CONCLUSION:
Results support the validity of this new global assessment
of symptom change. This measure is particularly useful for
assessing change over time when no baseline data are
available. Additional research should examine this measure's
responsiveness in the context of clinical
trials.},
Key = {fds87727}
}
@article{fds87746,
Author = {CR McCudden and VB Kraus},
Title = {Biochemistry of amino acid racemization and clinical
application to musculoskeletal disease.},
Journal = {Clinical biochemistry, United States},
Volume = {39},
Number = {12},
Pages = {1112-30},
Year = {2006},
Month = {December},
ISSN = {0009-9120},
Keywords = {Aging • Amino Acids • Biological Markers •
Collagen Type I • D-Aspartic Acid • Female •
Forensic Sciences • Humans • Male • Middle
Aged • Musculoskeletal Diseases • Stereoisomerism
• analysis • chemical synthesis • chemistry
• chemistry* • immunology • metabolism •
physiology • physiopathology*},
Abstract = {During aging, proteins are subject to numerous forms of
damage. Several types of non-enzymatic post-translational
modifications have been described in aging proteins,
including oxidation, nitration, glycation, and racemization.
Racemization of amino acids is the spontaneous conversion of
L-enantiomers to the D-form, which is dependent on
temperature, pH, and time. Because of the time-dependent
nature of racemization, it can be used to determine the
relative age and turnover rates of long-lived proteins.
There are many such long-lived proteins within the body;
they are found in the brain, eye, and heart, but are
particularly abundant in proteins found in musculoskeletal
tissues such as bone and cartilage. During disease,
musculoskeletal tissues have pathologically altered turnover
rates. Because turnover rates can be estimated from levels
of racemization, racemized musculoskeletal protein fragments
may serve as useful biomarkers of disease. This review
discusses the biochemistry of amino acid racemization in
proteins and its clinical application to musculoskeletal
disease.},
Key = {fds87746}
}
@article{fds87736,
Author = {H Betre and W Liu and MR Zalutsky and A Chilkoti and VB Kraus and LA
Setton},
Title = {A thermally responsive biopolymer for intra-articular drug
delivery.},
Journal = {Journal of controlled release : official journal of the
Controlled Release Society, Netherlands},
Volume = {115},
Number = {2},
Pages = {175-82},
Year = {2006},
Month = {October},
ISSN = {0168-3659},
Keywords = {Animals • Biopolymers • Delayed-Action
Preparations • Drug Delivery Systems* • Elastin
• Female • Half-Life • Injections,
Intra-Articular* • Isotope Labeling • Joints
• Peptides • Rats • Rats, Wistar •
Solubility • Temperature • chemical synthesis
• chemistry • chemistry* • metabolism •
pharmacokinetics},
Abstract = {Intra-articular drug delivery is the preferred standard for
targeting pharmacologic treatment directly to joints to
reduce undesirable side effects associated with systemic
drug delivery. In this study, a biologically based drug
delivery vehicle was designed for intra-articular drug
delivery using elastin-like polypeptides (ELPs), a
biopolymer composed of repeating pentapeptides that undergo
a phase transition to form aggregates above their transition
temperature. The ELP drug delivery vehicle was designed to
aggregate upon intra-articular injection at 37 degrees C,
and form a drug 'depot' that could slowly disaggregate and
be cleared from the joint space over time. We evaluated the
in vivo biodistribution and joint half-life of radiolabeled
ELPs, with and without the ability to aggregate, at
physiological temperatures encountered after intra-articular
injection in a rat knee. Biodistribution studies revealed
that the aggregating ELP had a 25-fold longer half-life in
the injected joint than a similar molecular weight protein
that remained soluble and did not aggregate. These results
suggest that the intra-articular joint delivery of ELP-based
fusion proteins may be a viable strategy for the prolonged
release of disease-modifying protein drugs for
osteoarthritis and other arthritides.},
Key = {fds87736}
}
@article{fds87733,
Author = {JL Huebner and VB Kraus},
Title = {Assessment of the utility of biomarkers of osteoarthritis in
the guinea pig.},
Journal = {Osteoarthritis and cartilage / OARS, Osteoarthritis Research
Society},
Volume = {14},
Number = {9},
Pages = {923-30},
Year = {2006},
Month = {September},
ISSN = {1063-4584},
url = {http://dx.doi.org/10.1016/j.joca.2006.03.007},
Keywords = {Age Factors • Animals • Biological Markers •
Cartilage, Articular • Chemokines • Collagen
• Cytokines • Disease Progression •
Extracellular Matrix Proteins • Glycoproteins •
Guinea Pigs • Keratan Sulfate • Linear Models
• Osteoarthritis • Sensitivity and Specificity
• Species Specificity • Synovial Fluid •
analysis • blood • chemistry* • immunology
• metabolism • metabolism*},
Abstract = {OBJECTIVE: To identify biochemical markers of osteoarthritis
(OA) in the guinea pig, we characterized four biomarkers and
17 cytokines for age- and strain-related differences.
METHODS: Two guinea pig strains were examined in this study:
(1) the Hartley (OA-prone) and (2) Strain 13 (OA-resistant).
Levels of synovial fluid keratan sulfate (KS) and cartilage
oligomeric matrix protein (COMP), as well as levels of serum
C2C, CPII, and a panel of cytokines and chemokines were
quantified in both guinea pig strains. These included: IL-1
alpha, IL-1 beta, IL-2, IL-3, IL-4, IL-5, IL-6, IL-10,
IL-12p40, IL-12p70, IL-17, G-CSF, GM-CSF, IFN-gamma, KC,
MIP-1 alpha, RANTES, and TNF-alpha. RESULTS: Synovial fluid
concentrations of KS and COMP increased coincident with
histological OA and correlated positively with the severity
of histological damage in both strains. Synovial fluid
concentrations of these biomarkers were elevated in the
knees of the Hartley compared to the Strain 13 animals, as
early as 2 months of age. From as early as 4 months of age,
the levels of serum C2C/CPII, representing the ratio of type
II collagen degradation and synthesis, were elevated in the
OA-prone Hartley compared with Strain 13 animals. Also, at
12 months of age, strain-related differences were apparent
for 11 of the 16 cytokines and chemokines. Using multiple
linear regression, serum IL-6 and TNF-alpha concentrations
were each strongly associated with strain, weight, and their
interaction (r2 = 0.80, P = 0.0002 for IL-6; r2 = 0.55, P =
0.02 for TNF-alpha). CONCLUSIONS: Biomarkers derived from
synovial fluid are reflective of histological severity in
the spontaneous model of OA in the guinea pig. The synovial
fluid biomarker profiles indicated accelerated cartilage
matrix turnover in the Hartley strain as early as 2 months
of age, prior to evidence of histological damage. The
Hartley strain also exemplified an imbalance in type II
collagen metabolism and a serum cytokine/chemokine profile
indicative of a pro-inflammatory state. These findings
elucidate additional disease-related features in the guinea
pig that have relevance to OA in humans.},
Language = {eng},
Doi = {10.1016/j.joca.2006.03.007},
Key = {fds87733}
}
@article{fds87718,
Author = {SY Kong and TV Stabler and LG Criscione and AL Elliott and JM Jordan and VB
Kraus},
Title = {Diurnal variation of serum and urine biomarkers in patients
with radiographic knee osteoarthritis.},
Journal = {Arthritis and rheumatism},
Volume = {54},
Number = {8},
Pages = {2496-504},
Year = {2006},
Month = {August},
ISSN = {0004-3591},
url = {http://dx.doi.org/10.1002/art.21977},
Keywords = {Aggrecans • Biological Markers • C-Reactive
Protein • Chondroitin Sulfate Proteoglycans •
Circadian Rhythm* • Collagen Type II •
Extracellular Matrix Proteins • Glycoproteins •
Humans • Hyaluronic Acid • Keratan Sulfate •
Lectins, C-Type • Osteoarthritis, Knee* •
Osteocalcin • Peptide Fragments • Procollagen
• Transforming Growth Factor beta • Transforming
Growth Factor beta1 • analysis • blood •
blood* • pathology • urine •
urine*},
Abstract = {OBJECTIVE: To evaluate diurnal variation of biomarkers in
subjects with osteoarthritis (OA) of the knee. METHODS:
Twenty subjects with radiographic knee OA were admitted to
the General Clinical Research Center of Duke University for
an overnight stay to undergo serial blood and urine
sampling. Biomarkers measured included serum hyaluronan
(HA), cartilage oligomeric matrix protein (COMP), keratan
sulfate (KS-5D4), aggrecan neoepitope (CS846),
high-sensitivity C-reactive protein (hsCRP), osteocalcin,
transforming growth factor beta1 (TGFbeta1), and type II
collagen (CII)-related epitopes (neoepitope from cleavage of
CII [C2C], carboxy-terminus of three-quarter peptide from
cleavage of CI and CII [C1,2C], and type II procollagen
carboxy-propeptide [CPII] in serum, and C-terminal
telopeptides of CII [CTX-II] and C2C in urine). RESULTS:
Levels of serum HA, COMP, KS-5D4, and TGFbeta1 increased
significantly from T0 (before arising from bed) to T1 (1
hour after arising). More diurnal variation in HA was
observed in patients with higher daily mean HA
concentrations. CPII increased significantly from T0 to T2
(4 hours after arising). Urinary concentrations of CTX-II
were also found to vary with morning activity, decreasing
significantly from T0 to T2. Urinary C2C concentrations
increased significantly from T0 until T3 (early evening). No
diurnal variations in CS846, hsCRP, osteocalcin, serum C2C,
or C1,2C were observed. Six biomarkers (serum C2C, C1,2C,
COMP, KS-5D4, TGFbeta1, and urinary CTX-II) were associated
with radiographic knee OA (expressed as the sum of
Kellgren/Lawrence radiographic severity grades), with the
strongest correlations observed with measurements obtained
at later time points (either T2 or T3). CONCLUSIONS: Our
study results suggest that serum and urine sampling for HA,
COMP, KS-5D4, TGFbeta1, CPII, urinary CTX-II, and urinary
C2C should be standardized in future OA clinical trials.
Serum and urine sampling at late midday time points may be
the optimal approach for OA studies, although this result
should be validated in a larger cohort.},
Language = {eng},
Doi = {10.1002/art.21977},
Key = {fds87718}
}
@article{fds87735,
Author = {DC Bauer and DJ Hunter and SB Abramson and M Attur and M Corr and D Felson and D Heinegård and JM Jordan and TB Kepler and NE Lane and T Saxne and B
Tyree, VB Kraus and Osteoarthritis Biomarkers
Network},
Title = {Classification of osteoarthritis biomarkers: a proposed
approach.},
Journal = {Osteoarthritis and cartilage / OARS, Osteoarthritis Research
Society},
Volume = {14},
Number = {8},
Pages = {723-7},
Year = {2006},
Month = {August},
ISSN = {1063-4584},
url = {http://dx.doi.org/10.1016/j.joca.2006.04.001},
Keywords = {Arthrography • Biological Markers • Disease
Progression • Humans • Odds Ratio •
Osteoarthritis • Prognosis • Rheumatology* •
Risk Factors • Treatment Outcome • analysis •
classification* • radiography •
therapy},
Abstract = {OBJECTIVE: Osteoarthritis (OA) biomarkers are needed by
researchers and clinicians to assist in disease diagnosis
and assessment of disease severity, risk of onset, and
progression. As effective agents for OA are developed and
tested in clinical studies, biomarkers that reliably mirror
or predict the progression or amelioration of OA will also
be needed. METHODS: The NIH-funded OA Biomarkers Network is
a multidisciplinary group interested in the development and
validation of OA biomarkers. This review summarizes our
efforts to characterize and classify OA biomarkers. RESULTS:
We propose the "BIPED" biomarker classification (which
stands for Burden of Disease, Investigative, Prognostic,
Efficacy of Intervention and Diagnostic), and offer
suggestions on optimal study design and analytic methods for
use in OA investigations. CONCLUSIONS: The BIPED
classification provides specific biomarker definitions with
the goal of improving our ability to develop and analyze OA
biomarkers, and to communicate these advances within a
common framework.},
Language = {eng},
Doi = {10.1016/j.joca.2006.04.001},
Key = {fds87735}
}
@article{fds87725,
Author = {VB Kraus},
Title = {Do biochemical markers have a role in osteoarthritis
diagnosis and treatment?},
Journal = {Best practice & research. Clinical rheumatology},
Volume = {20},
Number = {1},
Pages = {69-80},
Year = {2006},
Month = {February},
ISSN = {1521-6942},
url = {http://dx.doi.org/10.1016/j.berh.2005.09.001},
Keywords = {Animals • Biological Markers • Disease Progression
• Humans • Osteoarthritis • blood •
blood* • diagnosis* • therapy*},
Abstract = {It is possible to use biomarkers in cohort studies and in
clinical trials to increase our understanding of disease, to
elucidate disease mechanisms, and to bolster a clinical
impression of the disease state of osteoarthritis. Whether
it will be possible to utilize biomarkers meaningfully to
characterize the disease state in an individual patient
remains to be seen. Major concepts related to the use of
biomarkers for research and clinical practice, and factors
influencing biomarker concentrations, are described in this
review in order to address the potential role of biomarkers
in osteoarthritis diagnosis, prognosis, and
treatment.},
Language = {eng},
Doi = {10.1016/j.berh.2005.09.001},
Key = {fds87725}
}
@article{fds87729,
Author = {KD Allen and JM Jordan and JB Renner and VB Kraus},
Title = {Validity, factor structure, and clinical relevance of the
AUSCAN Osteoarthritis Hand Index.},
Journal = {Arthritis and rheumatism, United States},
Volume = {54},
Number = {2},
Pages = {551-6},
Year = {2006},
Month = {February},
ISSN = {0004-3591},
Keywords = {Aged • Disability Evaluation • Female • Hand
• Humans • Male • Osteoarthritis • Pain
Measurement • Questionnaires • Reproducibility of
Results • Rheumatology • Self Care • Severity
of Illness Index • diagnosis • methods •
methods* • physiopathology* • radiography •
standards • standards*},
Abstract = {OBJECTIVE: The Australian/Canadian (AUSCAN) Osteoarthritis
Hand Index is a self-report assessment of pain, stiffness,
and function in patients with hand osteoarthritis (OA).
Small studies have confirmed the reliability, construct
validity, and responsiveness of this measure, but the factor
structure has not been examined. In this study, we examined
the clinimetric properties and clinical relevance of the
AUSCAN index in a large sample of patients with familial
hand OA. METHODS: The study group comprised 700 patients
(80% female, mean age 69 years) who were part of a study on
the genetics of generalized OA. All patients had
radiographic hand OA bilaterally. The analyses examined
internal consistency, factor structure, and relationships of
the subscales to grip and pinch strength and a single-item
pain measure. RESULTS: Internal consistency was high for the
total AUSCAN index and the subscales (Cronbach's alpha =
0.93-0.96). The AUSCAN function subscale had the strongest
correlation with grip and pinch strength, and the pain
subscale had the strongest correlation with the single-item
pain measure, thus supporting the construct validity of
these subscales. Factor analysis showed that all pain and
function items clearly loaded on the subscale they were
intended to measure. Each 1-unit increase in the AUSCAN
function subscale was associated with a clinically relevant
decrease in hand strength. CONCLUSION: The results of this
study strongly confirm the clinimetric properties of the
AUSCAN index, including the validity of specific subscales.
Results indicate that the AUSCAN index can measure
meaningful changes in pain, stiffness, and
function.},
Key = {fds87729}
}
@article{fds87737,
Title = {McCudden C and VB Kraus. 2006. Biochemistry of amino
acid racemization and clinical application to
musculoskeletal disease. Clinical Biochemistry (in press).
},
Year = {2006},
Key = {fds87737}
}
@article{fds87749,
Title = {Birmingham, JD, V Vilim and VB Kraus. 2006. Collagen
biomarkers for arthritis applications. Biomarker Insights
2:61-76 (http://www.la-press.com/biomark.html).},
Year = {2006},
Key = {fds87749}
}
@article{fds87731,
Author = {JL Piscoya and B Fermor and VB Kraus and TV Stabler and F
Guilak},
Title = {The influence of mechanical compression on the induction of
osteoarthritis-related biomarkers in articular cartilage
explants.},
Journal = {Osteoarthritis and cartilage / OARS, Osteoarthritis Research
Society, England},
Volume = {13},
Number = {12},
Pages = {1092-9},
Year = {2005},
Month = {December},
ISSN = {1063-4584},
Keywords = {Animals • Biological Markers • Cartilage,
Articular • Chondroitin Sulfates • Extracellular
Matrix Proteins • Female • Glycoproteins •
Glycosaminoglycans • Keratan Sulfate •
Osteoarthritis • Radiopharmaceuticals • Stress,
Mechanical • Swine • analysis • biosynthesis*
• chemistry • etiology* • metabolism •
metabolism*},
Abstract = {OBJECTIVE: Macromolecules of the articular cartilage
extracellular matrix released into synovial fluid, blood, or
urine can serve as potentially useful biomarkers of the
severity of osteoarthritis (OA). Biomechanical factors play
an important role in OA pathogenesis, yet their influence on
biomarker production is not well understood. The goal of
this study was to examine the hypothesis that dynamic
mechanical stress influences the release of these biomarkers
from articular cartilage. METHODS: Explants of porcine
cartilage were subjected to dynamic compression at 0.5 Hz
for 24h at stresses ranging from 0.006 to 0.1 MPa. The
concentrations of cartilage oligomeric matrix protein
(COMP), keratan sulfate (KS measured as the 5 D 4 epitope),
total sulfated glycosaminoglycan (S-GAG), and the KS
(keratanase-digestible) and chondroitin sulfate (CS)
(chondroitinase-digestible) fractions of S-GAG were
measured. Radiolabel incorporation was used to determine the
rates of proteoglycan and protein synthesis. RESULTS: The
magnitudes of mechanical stress applied in this study
induced nominal tissue strains of 4-23%, consistent with a
range of physiological to hyperphysiologic strains measured
in situ. COMP release increased in proportion to the
magnitude of dynamic mechanical stress, while KS, CS and
total S-GAG release increased in a bimodal pattern with
increasing stress. Protein and proteoglycan synthesis were
significantly decreased at the highest level of stress.
CONCLUSION: Mechanical stress differentially regulates the
turnover of distinct pools of cartilage macromolecules.
These findings indicate that mechanical factors, independent
of exogenous cytokines or other stimulatory factors, can
influence the production and release of OA-related
biomarkers from articular cartilage.},
Key = {fds87731}
}
@article{fds87734,
Author = {F Eckstein and HC Charles and RJ Buck and VB Kraus and AE Remmers and M
Hudelmaier, W Wirth and JL Evelhoch},
Title = {Accuracy and precision of quantitative assessment of
cartilage morphology by magnetic resonance imaging at
3.0T.},
Journal = {Arthritis and rheumatism, United States},
Volume = {52},
Number = {10},
Pages = {3132-6},
Year = {2005},
Month = {October},
ISSN = {0004-3591},
Keywords = {Aged • Cartilage • Female • Femur •
Humans • Knee Joint • Magnetic Resonance Imaging
• Middle Aged • Osteoarthritis, Knee •
Reproducibility of Results • Tibia • methods*
• pathology* • standards*},
Abstract = {OBJECTIVE: Quantitative magnetic resonance imaging (MRI) of
articular cartilage represents a powerful tool in
osteoarthritis (OA) research, but has so far been confined
to a field strength of 1.5T. The aim of this study was to
evaluate the precision of quantitative MRI assessments of
human cartilage morphology at 3.0T and to correlate the
measurements at 3.0T with validated measurements at 1.5T.
METHODS: MR images of the knee of 15 participants with OA
and 15 healthy control subjects were acquired using Siemens
1.5T and 3.0T scanners. Double oblique coronal scans were
obtained at 1.5T with a 1.5-mm partition thickness, at 3.0T
with a 1.5-mm partition thickness, and at 3.0T with a 1.0-mm
partition thickness. Cartilage volume, thickness, and
surface area of the femorotibial cartilage plates were
quantified using proprietary software. RESULTS: For 1.5-mm
partition thickness at 1.5T, the precision error was 3.0%
and 2.6% for cartilage volume and cartilage thickness,
respectively. The error was smaller for a 1.5-mm partition
thickness at 3.0T (2.6% and 2.5%) and still smaller for a
1.0-mm partition thickness at 3.0T (2.1% and 2.0%).
Correlation coefficients between values obtained at 3.0T and
1.5T were high (r > or = 0.96), with no significant
deviation between the two field strengths. CONCLUSION:
Quantitative MRI measurement of cartilage morphology at 3.0T
(partition thickness 1 mm) was found to be accurate and
tended to be more reproducible than at 1.5T (partition
thickness 1.5 mm). Imaging at 3.0T may therefore provide
superior ability to detect changes in cartilage status over
time and to determine responses to treatment with
structure-modifying drugs.},
Key = {fds87734}
}
@article{fds87716,
Author = {VB Kraus},
Title = {Biomarkers in osteoarthritis.},
Journal = {Current opinion in rheumatology, United States},
Volume = {17},
Number = {5},
Pages = {641-6},
Year = {2005},
Month = {September},
ISSN = {1040-8711},
Keywords = {Biological Markers* • Humans • Osteoarthritis
• diagnosis* • physiopathology*},
Abstract = {PURPOSE OF REVIEW: Biomarker discovery and validation for
osteoarthritis have accelerated over the past several years,
coincident with an evolving understanding of joint tissue
molecules and their complex interactions, and the compelling
need for improved osteoarthritis outcome measures in
clinical trials. This review highlights advances in
osteoarthritis-related biomarker research within the past
year. RECENT FINDINGS: The studies in the past year
involving biochemical markers in humans can be assigned to
one of four categories: new approaches and new biomarkers,
exploratory studies in specialized disease subsets, large
cross-sectional validation studies, and longitudinal
studies, with and without an intervention. SUMMARY: Most
these studies have examined the association of a biomarker
with some aspect of the natural history of osteoarthritis.
As illustrated by the six studies reviewed here that
included therapeutic interventions, however, several
biomarkers are emerging that display credible association
with disease modification. The expanding pool of informative
osteoarthritis-related biomarkers is expected to positively
impact the development of therapeutics for this disease and,
it is hoped, ultimately clinical care.},
Key = {fds87716}
}
@article{fds87717,
Author = {LG Criscione and AL Elliott and T Stabler and JM Jordan and CF Pieper and VB Kraus},
Title = {Variation of serum hyaluronan with activity in individuals
with knee osteoarthritis.},
Journal = {Osteoarthritis and cartilage / OARS, Osteoarthritis Research
Society},
Volume = {13},
Number = {9},
Pages = {837-40},
Year = {2005},
Month = {September},
ISSN = {1063-4584},
url = {http://dx.doi.org/10.1016/j.joca.2005.05.004},
Keywords = {Aged • Aged, 80 and over • Biological Markers
• Eating* • Enzyme-Linked Immunosorbent Assay
• Exercise • Female • Humans •
Hyaluronic Acid • Linear Models • Male •
Middle Aged • Osteoarthritis, Knee • Sample Size
• Statistics, Nonparametric • blood • blood*
• methods • physiology*},
Abstract = {OBJECTIVE: Serum hyaluronan (HA) was evaluated for diurnal
variation in participants with osteoarthritis (OA) of the
knee. METHODS: Twenty participants with radiographic OA of
at least one knee were admitted overnight to the General
Clinical Research Center for serial serum sampling. Serum
was obtained between 6:00 p.m. and 8:00 p.m. on Day 1 (T3)
after a day of normal activity. During the night of bed
rest, participants remained supine for a minimum of 5 h
between the hours of 3:00 a.m. and 8:00 a.m. Blood was drawn
prior to arising from bed (T0), and 1h (T1) and 4 h (T2)
after arising and performing usual morning activities,
including eating breakfast. During the morning, participants
were encouraged to remain physically active and were not
permitted to sit for more than 30 min at a time. Serum HA
was measured by enzyme-linked immunosorbent assay. Results
were analyzed using non-parametric Freidman's test with
Dunn's post-hoc Multiple Comparison test. RESULTS: Serum
levels of HA increased significantly from T0 to T1 (P <
0.01). There were no other significant changes in serum HA
levels observed between any of the other time points.
CONCLUSIONS: Although a rise in serum HA with activity and
eating has been demonstrated previously in individuals with
rheumatoid arthritis, this is the first study to demonstrate
a similar rise in individuals with OA. These results suggest
that serum sampling for HA in OA clinical trials should be
performed more than 1h after arising in the morning and at
least 1h after breaking an overnight fast.},
Language = {eng},
Doi = {10.1016/j.joca.2005.05.004},
Key = {fds87717}
}
@article{fds87722,
Author = {RJ Lamers and JH van Nesselrooij and VB Kraus and JM Jordan and JB
Renner, AD Dragomir and G Luta and J van der Greef and J
DeGroot},
Title = {Identification of an urinary metabolite profile associated
with osteoarthritis.},
Journal = {Osteoarthritis and cartilage / OARS, Osteoarthritis Research
Society, England},
Volume = {13},
Number = {9},
Pages = {762-8},
Year = {2005},
Month = {September},
ISSN = {1063-4584},
Keywords = {Aged • Aged, 80 and over • Biological Markers
• Case-Control Studies • Female • Humans
• Joints • Least-Squares Analysis • Magnetic
Resonance Spectroscopy* • Male • Middle Aged
• Osteoarthritis • pathology • urine •
urine*},
Abstract = {OBJECTIVE: Osteoarthritis (OA) is one of the most common
diseases among the elderly. The main characteristic is the
progressive destruction of articular cartilage. We lack
quantitative and sensitive biomarkers for OA to detect
changes in the joints in an early stage of the disease. In
this study, we investigated whether a urinary metabolite
profile could be found that could serve as a diagnostic
biomarker for OA in humans. We also compared the profile we
obtained previously in the guinea pig spontaneous OA model.
METHODS: Urine samples of 92 participants (47 non-OA
controls and 45 individuals with radiographic OA of the
knees or hips) were selected from the Johnston County
Osteoarthritis Project (North Carolina, USA). Participants
ranged in age from 60 to 84 years. Samples were measured by
1H nuclear magnetic resonance spectroscopy (NMR) with
subsequent principal component discriminant analysis and
partial least squares regression analysis. RESULTS:
Differences were observed between urine NMR spectra of OA
cases and controls (P<0.001 for both male and female
subjects). A metabolite profile could be determined which
was strongly associated with OA. This profile largely
resembled the profile previously identified for guinea pigs
with OA (approximately 40 out of the approximately 125
signals of the human profile were present in the guinea pig
profile as well). A correlation was found between the
metabolite profile and radiographic OA severity (R2 = 0.82
(male); R2 = 0.93 (female)). CONCLUSION: This study showed
that a urine metabolite profile may serve as a novel
discriminating biomarker of OA.},
Key = {fds87722}
}
@article{fds87723,
Author = {AL McNulty and TV Stabler and TP Vail and GE McDaniel and VB
Kraus},
Title = {Dehydroascorbate transport in human chondrocytes is
regulated by hypoxia and is a physiologically relevant
source of ascorbic acid in the joint.},
Journal = {Arthritis and rheumatism, United States},
Volume = {52},
Number = {9},
Pages = {2676-85},
Year = {2005},
Month = {September},
ISSN = {0004-3591},
Keywords = {Arthritis, Rheumatoid • Ascorbic Acid • Biological
Transport • Cartilage, Articular • Cell Hypoxia
• Cells, Cultured • Chondrocytes •
Chromatography, High Pressure Liquid • Dehydroascorbic
Acid • Gene Expression • Knee Joint •
Monosaccharide Transport Proteins • Osteoarthritis,
Knee • RNA Interference • RNA, Messenger •
RNA, Small Interfering • Reverse Transcriptase
Polymerase Chain Reaction • Up-Regulation •
cytology • drug effects • metabolism •
metabolism* • pathology • pharmacology •
physiology},
Abstract = {OBJECTIVE: To evaluate the dehydroascorbate (DHA) transport
mechanisms in human chondrocytes. METHODS: The transport of
L-(14)C-DHA in human chondrocytes was analyzed under various
conditions, including the use of RNA interference (RNAi), to
determine the role of glucose transporter 1 (GLUT-1) and
GLUT-3 in L-14C-DHA transport and to evaluate the effects of
physiologically relevant oxygen tensions on L-14C-DHA
transport. In order to estimate the contributions of reduced
ascorbic acid (AA) and DHA to intracellular ascorbic acid
(Asc), the quantities of AA and DHA were measured in
synovial fluid samples from osteoarthritis (OA) patients and
compared with the reported levels in rheumatoid arthritis
(RA) patients. RESULTS: DHA transport in human chondrocytes
was glucose-sensitive, temperature-dependent, cytochalasin
B-inhibitable, modestly stereoselective for L-DHA, and
up-regulated by low oxygen tension. Based on the RNAi
results, GLUT-1 mediated, at least in part, the uptake of
DHA, whereas GLUT-3 had a minimal effect on DHA transport.
DHA constituted a mean 8% of the total Asc in the synovial
fluid of OA joints, in contrast to 80% of the reported total
Asc in RA joints. CONCLUSION: We provide the first evidence
that chondrocytes transport DHA via the GLUTs and that this
transport mechanism is modestly selective for L-DHA. In the
setting of up-regulated DHA transport at low oxygen
tensions, DHA would contribute 26% of the total
intracellular Asc in OA chondrocytes and 94% of that in RA
chondrocytes. These results demonstrate that DHA is a
physiologically relevant source of Asc for chondrocytes,
particularly in the setting of an inflammatory arthritis,
such as RA.},
Key = {fds87723}
}
@article{fds87713,
Author = {LM Boyd and WJ Richardson and J Chen and VB Kraus and A Tewari and LA
Setton},
Title = {Osmolarity regulates gene expression in intervertebral disc
cells determined by gene array and real-time quantitative
RT-PCR.},
Journal = {Annals of biomedical engineering, United
States},
Volume = {33},
Number = {8},
Pages = {1071-7},
Year = {2005},
Month = {August},
ISSN = {0090-6964},
Keywords = {Cells, Cultured • Female • Gene Expression
Profiling • Gene Expression Regulation • Humans
• Intervertebral Disk • Male • Middle Aged
• Oligonucleotide Array Sequence Analysis •
Osmolar Concentration • Reverse Transcriptase
Polymerase Chain Reaction • cytology • methods
• physiology*},
Abstract = {Intervertebral disc (IVD) cells experience a broad range of
physicochemical stimuli under physiologic conditions,
including alterations in their osmotic environment. Cellular
responses to altered osmolarity have been documented at the
transcriptional and post-translational level, but mainly for
extracellular matrix proteins. In this study, the gene
expression profile of human IVD cells was quantified with
gene array technology following exposure to increased
osmolarity in order to capture the biological responses for
a broad set of targets. A total of 42 genes were identified
in IVD cells as significantly changed following culture
under hyper-osmotic conditions. Gene expression patterns
were verified using RT-PCR. Genes identified in this study
include those related to cytoskeleton remodeling and
stabilization (ephrin-B2, muskelin), as well as membrane
transport (ion transporter SLC21A12, osmolyte transporter
SLC5A3, monocarboxylic acid SLC16A6). An unexpected finding
was the differential regulation of the gene for the
neurotrophin, brain-derived neurotrophic factor, by
hyper-osmotic stimuli that suggests a capability of IVD
cells to respond to physicochemical stimuli with factors
that may regulate discogenic pain.},
Key = {fds87713}
}
@article{fds87715,
Author = {J Chang and TL Kauf and S Mahajan and JM Jordan and VB Kraus and TP Vail and SD Reed and MA Omar and KH Kahler and KA Schulman},
Title = {Impact of disease severity and gastrointestinal side effects
on the health state preferences of patients with
osteoarthritis.},
Journal = {Arthritis and rheumatism, United States},
Volume = {52},
Number = {8},
Pages = {2366-75},
Year = {2005},
Month = {August},
ISSN = {0004-3591},
Keywords = {Aged • Anti-Inflammatory Agents, Non-Steroidal •
Female • Gastrointestinal Diseases • Health
Status* • Humans • Male • Middle Aged •
Osteoarthritis • Patient Satisfaction* • Severity
of Illness Index • adverse effects* • chemically
induced* • drug therapy* • physiopathology* •
therapeutic use},
Abstract = {OBJECTIVE: To describe the health state preferences of
patients with osteoarthritis (OA) according to the level of
pain and disability and the extent of gastrointestinal side
effects from nonsteroidal antiinflammatory drugs (NSAIDs).
METHODS: Using combinations of 5 OA health states (4
specifying medication use) and 6 gastrointestinal side
effect profiles, we developed 25 scenarios. In an Internet
survey, adults with OA evaluated 5 randomly chosen health
state-side effect scenarios (in addition to scenarios for
congestive heart failure and wearing dentures, as
benchmarks). They rated the scenarios on a 0-100 scale, in
which 100 corresponds to best imaginable health. Unadjusted
mean ratings were calculated using a difference-in-difference
approach. A generalized linear model was used to estimate
the effects of disease severity and side effect severity on
the ratings, after controlling for patient characteristics.
RESULTS: A total of 4,386 respondents whose mean age was
55.3 years, of whom 3,107 (70.8%) were women and 4,007
(91.4%) were white, completed the survey. Mean adjusted
ratings for health state-side effect scenarios ranged from
94.9 for the mildest scenario to 25.3 for the most severe
scenario. Severity of NSAID side effects had a greater
negative influence on the ratings in milder OA states than
in more severe OA states. Ratings were lower among men (P <
0.001) and among respondents with OA pain in the previous 24
hours (P < 0.001). Disease severity had a greater effect on
ratings than did side effect severity. CONCLUSION: Patients
consider pain and functional limitations associated with OA
to be important determinants of well-being. Future research
should attempt to determine whether patients prefer
reductions in their OA-related pain and disability over
improvements in treatment side effect profiles.},
Key = {fds87715}
}
@article{fds87724,
Author = {AL McNulty and TP Vail and VB Kraus},
Title = {Chondrocyte transport and concentration of ascorbic acid is
mediated by SVCT2.},
Journal = {Biochimica et biophysica acta, Netherlands},
Volume = {1712},
Number = {2},
Pages = {212-21},
Year = {2005},
Month = {June},
ISSN = {0006-3002},
Keywords = {Amino Acids • Ascorbic Acid • Cartilage •
Cell Survival • Chondrocytes • Chromatography,
High Pressure Liquid • Dehydroascorbic Acid •
Glucose • Humans • Kinetics • Organic Anion
Transporters, Sodium-Dependent • RNA • RNA
Interference • Reverse Transcriptase Polymerase Chain
Reaction • Sodium • Sulfinpyrazone •
Symporters • Temperature • Time Factors •
chemistry • chemistry* • metabolism •
metabolism* • pharmacology • physiology*},
Abstract = {Collagen II is the major protein component of articular
cartilage and forms the collagen fibril network, which
provides the tensile strength of cartilage. Collagen II
synthesis is enhanced by ascorbic acid (vitamin C) at both a
transcriptional and post-transcriptional level. While the
importance of ascorbic acid in the synthesis of collagen has
been established, the mechanism by which this essential
nutrient is transported into chondrocytes has not been
investigated previously. We have characterized the transport
of the reduced form of ascorbic acid in passaged primary
human chondrocytes to discern the physiologically relevant
pathways of ascorbic acid transport in cartilage. We have
found that chondrocytes are robust concentrators of ascorbic
acid, capable of transporting the reduced form, and
concentrating total ascorbic acid, in the reduced form and
its metabolites, 960-fold over the concentration in the
extracellular milieu. Chondrocyte transport of ascorbic acid
was sodium and temperature dependent, stereoselective for
the L-forms, and inhibited by the anion transport inhibitor,
sulfinpyrazone. Chondrocytes preferentially expressed the
full-length and functional isoform of sodium-dependent
vitamin C transporter 2 (SVCT2). When this transcript was
suppressed with sequence-specific siRNAs, the active
transport component of ascorbic acid was abolished. Thus, we
provide the first evidence that SVCT2 mediates the secondary
active and concentrative transport of ascorbic acid in human
chondrocytes.},
Key = {fds87724}
}
@article{fds87732,
Author = {VB Kraus and TP Vail and T Worrell and G McDaniel},
Title = {A comparative assessment of alignment angle of the knee by
radiographic and physical examination methods.},
Journal = {Arthritis and rheumatism, United States},
Volume = {52},
Number = {6},
Pages = {1730-5},
Year = {2005},
Month = {June},
ISSN = {0004-3591},
Keywords = {Aged • Biomechanics • Female • Humans •
Knee Joint • Male • Middle Aged •
Osteoarthritis, Knee • Physical Examination •
Trabeculectomy • anatomy & histology • diagnosis*
• methods • radiography •
radiography*},
Abstract = {OBJECTIVE: To compare the knee-alignment angle from a
full-limb radiograph (mechanical axis) with the
anatomic-axis angle as measured by physical examination
using a goniometer and by 2 other radiographic methods.
METHODS: The knee-alignment angle was measured in 114 knees
of 57 subjects who had radiographic osteoarthritis (OA),
with a Kellgren/Lawrence grade of >/=1 in at least one knee.
The mechanical axis was defined as the angle formed by the
intersection of 2 lines, one from the center of the head of
the femur to the center of the tibial spines, and a second
from the center of the talus to the center of the tibial
spines. The anatomic axis was defined as the angle formed by
2 lines, each originating from a point bisecting the femur
and tibia and converging at the center of the tibial spine
tips. The anatomic-axis angle was measured by 3 methods: 1)
physical examination using a goniometer, 2) a
posteroanterior (PA) fixed-flexion knee radiograph
(anatomic(PA) axis), and 3) an anteroposterior (AP)
full-limb radiograph (anatomic(AP) axis). RESULTS:
Significant correlations were found between the
mechanical-axis angle and the anatomic-axis angle measured
by each of the 3 methods: by goniometer (r = 0.70, P <
0.0001), by anatomic(PA) axis (r = 0.75, P < 0.0001), and by
anatomic(AP) axis (r = 0.65, P < 0.0001). The anatomic axis
was offset a mean 4.21 degrees valgus from the mechanical
axis (3.5 degrees in women, 6.4 degrees in men), which was
consistent across all methods. CONCLUSION: Knee alignment
assessed clinically by goniometer or measured on a knee
radiograph is correlated with the angle measured on the more
cumbersome and costly full-limb radiograph. These
alternative measures have the potential to provide useful
information regarding the risk of progression of knee OA
when a full-limb radiograph is not available.},
Key = {fds87732}
}
@article{fds87719,
Author = {KL Dominick and JM Jordan and JB Renner and VB Kraus},
Title = {Relationship of radiographic and clinical variables to pinch
and grip strength among individuals with
osteoarthritis.},
Journal = {Arthritis and rheumatism, United States},
Volume = {52},
Number = {5},
Pages = {1424-30},
Year = {2005},
Month = {May},
ISSN = {0004-3591},
Keywords = {Aged • Female • Hand Strength* • Hand* •
Humans • Male • Middle Aged • Multivariate
Analysis • Osteoarthritis • Severity of Illness
Index • physiopathology* • radiography*},
Abstract = {OBJECTIVE: Little is known about how specific radiographic
features are related to hand strength in osteoarthritis
(OA). This study examined associations of radiographic
variables with pinch and grip strength among individuals
with radiographic hand OA. METHODS: Participants (n = 700,
80% female, mean age 69 years) were part of a study on the
genetics of generalized OA. All had bilateral radiographic
hand OA. Linear models were used to examine associations of
grip and pinch strength with 1) OA in joint groups (proximal
interphalangeal, metacarpophalangeal [MCP], carpometacarpal
[CMC]), 2) OA in rays (first through fifth), and 3) summed
Kellgren/Lawrence (K/L) grades for severity of OA in all
joints. Adjusted models controlled for age, sex, hand pain,
chondrocalcinosis, and hand hypermobility. Mixed models
accounted for clustering within families. RESULTS: In
bivariate analyses, all joint groups, all rays, and total
summed K/L grades were significantly negatively associated
with grip and pinch strength (P < 0.05). In adjusted models,
the only joint group significantly associated with grip
strength was the CMCs, and only OA in the MCP joint was
significantly associated with pinch strength (P < 0.05). The
only ray significantly associated with grip strength (P <
0.05) was ray 1, and no individual rays were significantly
associated with pinch strength. A higher summed K/L grade
was significantly associated with both lower grip strength
and lower pinch strength. CONCLUSION: Among individuals with
radiographic hand OA, increasing radiographic severity is
associated with reduced grip and pinch strength, even when
controlling for self-reported pain. Individuals with
radiographic OA in specific locations (CMC joints, MCP
joints, and ray 1) may be at particular risk for reduced
hand strength.},
Key = {fds87719}
}
@article{fds87730,
Author = {AL Elliott and VB Kraus and G Luta and T Stabler and JB Renner and J
Woodard, AD Dragomir and CG Helmick and MC Hochberg and JM
Jordan},
Title = {Serum hyaluronan levels and radiographic knee and hip
osteoarthritis in African Americans and Caucasians in the
Johnston County Osteoarthritis Project.},
Journal = {Arthritis and rheumatism, United States},
Volume = {52},
Number = {1},
Pages = {105-11},
Year = {2005},
Month = {January},
ISSN = {0004-3591},
Keywords = {African Americans* • Aging • Arthrography* •
Biological Markers • Cross-Sectional Studies •
European Continental Ancestry Group* • Female •
Hip Joint • Humans • Hyaluronic Acid • Knee
Joint • Male • Middle Aged • Osteoarthritis
• Prospective Studies • Sex Characteristics •
blood • blood* • ethnology • radiography
• radiography*},
Abstract = {OBJECTIVE: Serum hyaluronan (HA) has been proposed as a
potential biomarker of osteoarthritis (OA). We examined
associations between serum HA and radiographic OA in an
ethnically diverse, population-based sample. METHODS:
Participants were selected from the Johnston County
Osteoarthritis Project, using stratified simple random
sampling to achieve balance according to radiographic knee
OA status, ethnic group, sex, and age group. Serum HA was
measured by enzyme-linked immunosorbent assay. Radiographic
OA variables included knee OA, knee OA laterality, knee OA
severity, concomitant knee and hip OA, and total number of
OA-affected knee and hip joints. Analysis of covariance was
used to assess differences in mean serum levels of natural
log-transformed HA (ln serum HA) between groups, adjusting
for ethnicity, sex, age, body mass index (BMI), and
self-reported comorbidities. RESULTS: Levels of ln serum HA
were positively associated with all definitions of
radiographic OA (P < 0.0001). Levels of ln serum HA were
higher in Caucasians (P = 0.0094) and in men (P = 0.0038)
and were moderately correlated with age (r = 0.35, P <
0.0001). The associations with radiographic OA, ethnicity,
sex, and age remained statistically significant after
adjustment (P < 0.0045). There were no interactions between
ethnicity and the other covariates. CONCLUSION: These
cross-sectional data support a role for serum HA as a
biomarker of radiographic OA. The variations in levels of
serum HA attributable to ethnicity, sex, and age were not
explained by radiographic OA, BMI, or comorbidities. The
lack of strong confounding between serum HA and
comorbidities further supports a role for serum HA as a
potential biomarker.},
Key = {fds87730}
}
@article{fds87712,
Author = {T Stabler and JC Piette and X Chevalier and A Marini-Portugal and VB
Kraus},
Title = {Serum cytokine profiles in relapsing polychondritis suggest
monocyte/macrophage activation.},
Journal = {Arthritis and rheumatism, United States},
Volume = {50},
Number = {11},
Pages = {3663-7},
Year = {2004},
Month = {November},
ISSN = {0004-3591},
Keywords = {Adult • Aged • Arthritis, Rheumatoid •
Autoimmunity* • Case-Control Studies • Chemokine
CCL2 • Cytokines • Female • Humans •
Interleukin-8 • Macrophage Inflammatory Protein-1
• Macrophages • Male • Middle Aged •
Monocytes • Polychondritis, Relapsing • blood
• blood* • immunology*},
Abstract = {OBJECTIVE: There is evidence that autoimmunity plays a
significant role in the pathogenesis of relapsing
polychondritis (RP). This study was designed to investigate
circulating levels of various cytokines in relation to the
etiology of this rare disorder, and to compare the pattern
of cytokine elevations in RP with that in another autoimmune
disease, rheumatoid arthritis (RA). METHODS: Serum from 22
patients with active RP and an equal number of age- and
sex-matched healthy controls and RA patients were available
for analysis. The following cytokines were measured:
interleukin-1beta (IL-1beta), IL-2, IL-4, IL-5, IL-6, IL-7,
IL-8, IL-10, IL-12, IL-13, IL-17, interferon-gamma
(IFNgamma), tumor necrosis factor alpha, granulocyte
colony-stimulating factor (G-CSF), granulocyte-macrophage
colony-stimulating factor (GM-CSF), monocyte chemoattractant
protein 1 (MCP-1), and macrophage inflammatory protein 1beta
(MIP-1beta). Results were analyzed by nonparametric
Mann-Whitney test with Holm stepdown adjustment for multiple
testing. RESULTS: The levels of 3 of these cytokines showed
significant differences between RP patients and controls.
Compared with controls, mean serum levels of MCP-1,
MIP-1beta, and IL-8 were all much higher in patients with
active RP. In contrast, RA patients showed a more general
increase in all cytokines measured, with much higher levels
of IL-2, IL-4, IL-5, IL-6, IL-7, IL-10, IL-13, IFNgamma,
G-CSF, GM-CSF, MCP-1, and MIP-1beta compared with controls.
CONCLUSION: Levels of 3 serum cytokines were significantly
higher in RP patients than in age- and sex-matched controls.
One of these 3 cytokines, IL-8, was not significantly
elevated in RA samples. Overall, in RP, a more discrete
group of cytokines exhibited significantly increased levels
than was found in RA. Each of the 3 cytokines that were
elevated in RP is a proinflammatory chemokine,
characteristic of activation of the monocyte and macrophage
lineage, and in the case of IL-8, also of neutrophils. These
data suggest a major role for a cell-mediated immune
response in the pathophysiology of RP.},
Key = {fds87712}
}
@article{fds87726,
Author = {LM Boyd and J Chen and VB Kraus and LA Setton},
Title = {Conditioned medium differentially regulates matrix protein
gene expression in cells of the intervertebral
disc.},
Journal = {Spine, United States},
Volume = {29},
Number = {20},
Pages = {2217-22},
Year = {2004},
Month = {October},
ISSN = {1528-1159},
Keywords = {Aggrecans • Animals • Cartilage • Cell
Lineage • Cells, Cultured • Collagen Type I •
Collagen Type II • Culture Media, Conditioned •
Cytokines • Extracellular Matrix Proteins • Gene
Expression Regulation • Growth Substances •
Intervertebral Disk • Lectins, C-Type • Lumbar
Vertebrae • Notochord • Organ Specificity •
Proteoglycans • RNA, Messenger • Reverse
Transcriptase Polymerase Chain Reaction • Sus scrofa
• biosynthesis • biosynthesis* • cytology
• drug effects • drug effects* • genetics
• metabolism • pharmacology • pharmacology*
• secretion • secretion* •
ultrastructure},
Abstract = {STUDY DESIGN: Matrix protein gene expression was determined
for cells of the anulus fibrosus (AF) and nucleus pulposus
(NP) regions of the intervertebral disc when cultured in AF
or NP cell-conditioned medium. OBJECTIVES: To investigate
changes in mRNA levels for type I collagen, type II collagen
and aggrecan in cells of the AF and NP in response to
cell-conditioned medium. SUMMARY OF BACKGROUND DATA: Cells
of the intervertebral disc have been shown to respond to
exogenous soluble mediators such as the growth factors
TGF-beta and IGF-1. Little is known of their biologic
response to endogenous factors that may be secreted locally
or by cells of neighboring regions. METHODS: Porcine cells
were cultured for 48 hours in alginate gel in the presence
or absence of conditioned medium. Gene expression for
aggrecan and collagens was quantified using real-time
reverse transcriptase-polymerase chain reaction. RESULTS.:
AF cell gene expression was generally stimulated by the
conditioned medium of either AF or NP cells. In contrast,
the notochordal cell-containing NP cells showed little
change in gene expression with either source of conditioned
medium. CONCLUSIONS: Cells of the NP and AF secrete soluble
factors in culture at similarly effective doses to stimulate
matrix protein gene expression in AF cells of the
intervertebral disc. Unlike AF cells, however, NP cell gene
expression was not stimulated by any conditioned medium,
suggesting that differences exist in the responsiveness of
cells of notochordal (NP) and fibrocartilaginous (AF)
phenotypes. Understanding these differences between cells of
the intervertebral disc may reveal unique stimulatory
factors important to repair and regeneration of the
degenerated intervertebral disc.},
Key = {fds87726}
}
@article{fds87704,
Author = {G Varjú and CF Pieper and JB Renner and VB Kraus},
Title = {Assessment of hand osteoarthritis: correlation between
thermographic and radiographic methods.},
Journal = {Rheumatology (Oxford, England), England},
Volume = {43},
Number = {7},
Pages = {915-9},
Year = {2004},
Month = {July},
ISSN = {1462-0324},
Keywords = {Aged • Aged, 80 and over • Analysis of Variance
• Body Temperature • Cross-Sectional Studies
• Disease Progression • Female • Finger Joint
• Humans • Male • Middle Aged •
Osteoarthritis • Signal Processing, Computer-Assisted
• Thermography • diagnosis* • pathology*
• radiography},
Abstract = {OBJECTIVE: Anatomical stages of digital osteoarthritis (OA)
have been characterized radiographically as progressing
through sequential phases from normal to osteophyte
formation, progressive loss of joint space, joint erosion
and joint remodelling. Our study was designed to evaluate a
physiological parameter, joint surface temperature, measured
with computerized digital infrared thermal imaging, and its
association with sequential stages of radiographic OA (rOA).
METHODS: Thermograms, radiographs and digital photographs
were taken of both hands of 91 subjects with nodal hand OA.
Temperature measurements were made on digits 2-5 at distal
interphalangeal (DIP) joints, proximal interphalangeal (PIP)
joints and metacarpophalangeal (MCP) joints (2184 joints in
total). We fitted a repeated measures ANCOVA model to
analyse the effects of rOA on temperature, with handedness,
joint group, digit and NSAID use as covariates. RESULTS: The
reliability of the thermoscanning procedure was high
(generalizability coefficient 0.899 for two scans performed
3 h apart). The mean joint temperature decreased with
increasing rOA severity, defined by the Kellgren-Lawrence
(KL) scale. The mean temperature of KL0 joints was
significantly different from that of each of the other KL
grades (P </= 0.002). After adjustment for the other
covariates, there was a strong association of rOA with joint
surface temperature (P<0.001). The earliest discernible
radiographic disease (KL1) was associated with a higher
surface temperature than KL0 joints (P = 0.01) and a higher
surface temperature than any other KL grade. Joint erosions
were not associated with a change in joint temperature.
CONCLUSION: Joint surface temperature varied with the
severity of rOA. Joints were warmer than normal at the onset
of OA. As the severity of rOA worsened, joint surface
temperature declined. These data support the supposition
that digital OA progresses in phases initiated by an
inflammatory process. The cooler surface temperatures in
later stages of the disease may in part explain the paucity
of symptoms reported by patients with hand
OA.},
Key = {fds87704}
}
@article{fds87714,
Author = {VB Kraus and YJ Li and ER Martin and JM Jordan and JB Renner and M Doherty and AG Wilson and R Moskowitz and M Hochberg and R Loeser and M Hooper and S
Sundseth},
Title = {Articular hypermobility is a protective factor for hand
osteoarthritis.},
Journal = {Arthritis and rheumatism, United States},
Volume = {50},
Number = {7},
Pages = {2178-83},
Year = {2004},
Month = {July},
ISSN = {0004-3591},
Keywords = {Adult • Aged • Aged, 80 and over •
Arthrography* • Carpal Bones • Cohort Studies
• Female • Finger Joint • Hand* • Humans
• Joint Instability • Logistic Models • Male
• Metacarpus • Middle Aged • Odds Ratio
• Osteoarthritis • Wrist • complications*
• diagnosis • genetics • radiography •
radiography*},
Abstract = {OBJECTIVE: Very few studies have evaluated the association
of articular hypermobility and radiographic osteoarthritis
(OA) in humans. We assessed hypermobility and its
relationship to radiographic hand OA in a family-based
study. METHODS: A total of 1,043 individuals were enrolled
in the multicenter Genetics of Generalized Osteoarthritis
study, in which families were required to have 2 siblings
with radiographic OA involving >/=3 joints (distributed
bilaterally) of the distal interphalangeal (DIP), proximal
interphalangeal (PIP), or carpometacarpal (CMC) joint
groups, and OA in at least one DIP joint. Radiographic OA
was defined as a score of >/=2 on the Kellgren/Lawrence
scale in one or more joints within the group. The Beighton
criteria for assessment of hypermobility were recorded on a
0-9-point scale. Hypermobility was defined as a Beighton
score of >/=4, a threshold generally used to establish a
clinical diagnosis of joint laxity. A threshold of >/=2 was
also evaluated to assess lesser degrees of hypermobility.
The Beighton score for the present was calculated based on
clinical examination, and that for the past was based on
recall of childhood hypermobility in the first 2 decades of
life. The association of hypermobility and radiographic OA
of the PIP, CMC, and metacarpophalangeal joints was
evaluated in all participants and in men and women
separately. Multiple logistic regression was used to examine
the relationship of hypermobility with radiographic OA in
each joint group, after adjusting for age and sex. The
association of hypermobility and DIP OA was not evaluated,
because evidence of DIP OA was required for study inclusion.
RESULTS: Using a threshold Beighton score of 4, 3.7% of
individuals were classified as hypermobile based on the
present examination, and 7.4% were classified as hypermobile
based on the past assessment. A significant negative
association between present hypermobility and age was
observed. In persons with hypermobility, the odds of OA in
PIP joints was lower (for present, odds ratio [OR] 0.34, 95%
confidence interval [95% CI] 0.16-0.71; for past, OR 0.43,
95% CI 0.24-0.78). Similar results were obtained using a
threshold Beighton score of 2. The lower odds of PIP OA with
hypermobility were significant after adjusting for sex and
age (for present, OR 0.44, 95% CI 0.20-0.94; for past, OR
0.48, 95% CI 0.26-0.87). CONCLUSION: This study demonstrated
a joint-protective effect of hypermobility for radiographic
OA of PIP joints. In contrast to previous studies showing an
association of hypermobility and CMC OA, in this cohort
there was no evidence for increased odds of OA in any joint
group of the hand in association with articular
hypermobility.},
Key = {fds87714}
}
@article{fds87720,
Author = {F Guilak and B Fermor and FJ Keefe and VB Kraus and SA Olson and DS
Pisetsky, LA Setton and JB Weinberg},
Title = {The role of biomechanics and inflammation in cartilage
injury and repair.},
Journal = {Clinical orthopaedics and related research, United
States},
Number = {423},
Pages = {17-26},
Year = {2004},
Month = {June},
ISSN = {0009-921X},
Keywords = {Animals • Biomechanics • Cartilage, Articular
• Humans • Inflammation • Inflammation
Mediators • Osteoarthritis • Wound Healing •
injuries* • metabolism • physiology •
physiopathology • physiopathology*},
Abstract = {Osteoarthritis is a painful and debilitating disease
characterized by progressive degenerative changes in the
articular cartilage and other joint tissues. Biomechanical
factors play a critical role in the initiation and
progression of this disease, as evidenced by clinical and
animal studies of alterations in the mechanical environment
of the joint caused by trauma, joint instability, disuse, or
obesity. The onset of these changes after joint injury
generally has been termed posttraumatic arthritis and can be
accelerated by factors such as a displaced articular
fracture. Within this context, there is considerable
evidence that interactions between biomechanical factors and
proinflammatory mediators are involved in the progression of
cartilage degeneration in posttraumatic arthritis. In vivo
studies have shown increased concentrations of inflammatory
cytokines and mediators in the joint in mechanically induced
models of osteoarthritis. In vitro explant studies confirm
that mechanical load is a potent regulator of matrix
metabolism, cell viability, and the production of
proinflammatory mediators such as nitric oxide and
prostaglandin E2. Knowledge of the interaction of
inflammatory and biomechanical factors in regulating
cartilage metabolism would be beneficial to an understanding
of the etiopathogenesis of posttraumatic osteoarthritis and
in the improvement of therapies for joint
injury.},
Key = {fds87720}
}
@article{fds87728,
Author = {VB Kraus and JL Huebner and T Stabler and CM Flahiff and LA Setton and C
Fink, V Vilim and AG Clark},
Title = {Ascorbic acid increases the severity of spontaneous knee
osteoarthritis in a guinea pig model.},
Journal = {Arthritis and rheumatism, United States},
Volume = {50},
Number = {6},
Pages = {1822-31},
Year = {2004},
Month = {June},
ISSN = {0004-3591},
Keywords = {Animals • Antioxidants • Ascorbic Acid • Bone
Density • Cartilage • Collagen • Disease
Models, Animal • Extracellular Matrix Proteins •
Glycoproteins • Guinea Pigs • Least-Squares
Analysis • Male • Osteoarthritis, Knee •
Scurvy • Severity of Illness Index • Synovial
Fluid • Transforming Growth Factor beta • Weight
Gain • blood • drug effects* • metabolism
• pathology • pharmacology* •
physiopathology* • prevention & control},
Abstract = {OBJECTIVE: To determine whether ascorbic acid might be of
benefit for the treatment of spontaneous osteoarthritis (OA)
when administered over a long period of time. METHODS: We
investigated the effects of 8 months' exposure to low,
medium, and high doses of ascorbic acid on the in vivo
development of histologic knee OA in the male Hartley guinea
pig. The low dose represented the minimum amount needed to
prevent scurvy. The medium dose was the amount present in
standard laboratory guinea pig chow and resulted in plasma
levels comparable with those achieved in a person consuming
200 mg/day (5 fruits and vegetables daily). The high dose
was the amount shown in a previous study of the guinea pig
to slow the progression of surgically induced OA. RESULTS:
We found an association between ascorbic acid
supplementation and increased cartilage collagen content
but, in contrast to findings in a previous study of
surgically induced OA in the guinea pig, ascorbic acid
worsened the severity of spontaneous OA. Active transforming
growth factor beta (TGF beta) was expressed in marginal
osteophytes, whose size and number were significantly
increased with increasing intake of ascorbic acid. Synovial
fluid levels of cartilage oligomeric matrix protein, a
biomarker of cartilage turnover, corroborated the histologic
findings. CONCLUSION: Ascorbic acid has been shown to
activate latent TGF beta. Prolonged intraarticular exposure
to TGF beta has been shown to cause OA-like changes. We
found expression of active TGF beta in osteophytes, a
prominent feature of the joint histology seen in association
with ascorbic acid treatment. Thus, the deleterious effects
of prolonged ascorbic acid exposure may be mediated in part
by TGF beta. This worsening of OA with ascorbic acid
supplementation suggests that ascorbic acid intake should
not be supplemented above the currently recommended dietary
allowance (90 mg/day for men and 75 mg/day for
women).},
Key = {fds87728}
}
@article{fds87703,
Author = {CM Flahiff and VB Kraus and JL Huebner and LA Setton},
Title = {Cartilage mechanics in the guinea pig model of
osteoarthritis studied with an osmotic loading
method.},
Journal = {Osteoarthritis and cartilage / OARS, Osteoarthritis Research
Society, England},
Volume = {12},
Number = {5},
Pages = {383-8},
Year = {2004},
Month = {May},
ISSN = {1063-4584},
Keywords = {Animals • Cartilage Diseases • Cartilage,
Articular • Elasticity • Guinea Pigs • Knee
Joint • Male • Osmotic Pressure •
Osteoarthritis • Patella • Stress, Mechanical
• Tensile Strength • Tibia • physiology
• physiology* • physiopathology*},
Abstract = {OBJECTIVE: To determine the material properties of articular
cartilage in the Hartley guinea pig model of spontaneous
osteoarthritis. METHODS: Cartilage-bone samples from the
medial femoral condyle and tibial plateau of 12 month-old
guinea pig knees were subjected to osmotic loading.
Site-matched swelling strains and fixed charge density
values were used in a triphasic theoretical model for
cartilage swelling to determine the modulus of the cartilage
solid matrix. The degree of cartilage degeneration was
assessed in adjacent tissue sections using a
semi-quantitative histological grading scheme. RESULTS:
Decreased values for both moduli and surface zone fixed
charge density were associated with increasing grades of
cartilage degeneration. Decreases in moduli reflect damage
to the collagen matrix, which give rise to greater swelling
strains. CONCLUSION: Histological evidence of cartilage
degeneration was associated with impaired cartilage
mechanics in the aging Hartley guinea pig.},
Key = {fds87703}
}
@article{fds87705,
Author = {JM Jordan and VB Kraus and MC Hochberg},
Title = {Genetics of osteoarthritis.},
Journal = {Current rheumatology reports, United States},
Volume = {6},
Number = {1},
Pages = {7-13},
Year = {2004},
Month = {February},
ISSN = {1523-3774},
Keywords = {Biomedical Research • Chromosome Mapping* • Humans
• Linkage (Genetics)* • Osteoarthritis •
Pedigree • Protein Array Analysis • Twin Studies
• genetics*},
Abstract = {Osteoarthritis (OA) is a major cause of morbidity, physical
limitation, and health care use, including total joint
arthroplasty. That OA has a genetic component has been known
for some time, but only recently has formal study of this
occurred. Twin studies, segregation analyses, linkage
analyses, and candidate gene association studies have
generated important information about inheritance patterns
and the location in the genome of potentially causative
mutations. Results across studies are not always concordant,
however; this is likely the result of variations in study
populations, disease definitions, evaluation of control
subjects, and statistical analysis. Although the genetics of
OA is complex and not completely understood, there is cause
for optimism as rapidly improving technologies make the
quest for the genes responsible for OA increasingly within
reach. Family history of OA and joint replacement for OA
should be assessed in the context of other potentially
modifiable risk factors to attempt to alter patient
outcome.},
Key = {fds87705}
}
@article{fds87707,
Author = {VB Kraus and T Stabler and ET Le and M Saltarelli and NB
Allen},
Title = {Urinary type II collagen neoepitope as an outcome measure
for relapsing polychondritis.},
Journal = {Arthritis and rheumatism, United States},
Volume = {48},
Number = {10},
Pages = {2942-8},
Year = {2003},
Month = {October},
ISSN = {0004-3591},
Keywords = {Adolescent • Biological Markers • Collagen Type II
• Epitopes • Humans • Male • Outcome
Assessment (Health Care) • Polychondritis, Relapsing
• diagnosis* • urine • urine*},
Abstract = {Herein we describe the case of a man who was diagnosed as
having relapsing polychondritis (RP) when he was 18 years of
age and was treated over the course of 2 years with numerous
immunosuppressive agents, including tumor necrosis factor
alpha (TNFalpha) inhibitors. His respiratory symptoms were
refractory to treatment. Serum and urine samples were
obtained periodically for measurement of erythrocyte
sedimentation rate (ESR), C-reactive protein (CRP) levels,
anti-type II collagen (anti-CII) antibodies, and urinary
type II collagen neoepitope (uTIINE) levels. The uTIINE
assay is specific for collagenase cleavage products CII
present in urine. ESRs and CRP levels varied widely but were
rarely normal. Anti-CII antibody titers were high initially
and decreased slowly and steadily for a year following the
start of immunosuppressive medication, remaining low
throughout the remainder of the patient's monitored disease
course. The uTIINE levels were elevated prior to the
initiation of TNFalpha inhibitors. Upon initiation of
etanercept, they decreased abruptly to normal and stayed
nearly normal. The uTIINE levels rose abruptly again upon
discontinuation of TNFalpha inhibitor treatment. The
dramatic decline in CII degradation, coincident with the
administration of the TNFalpha inhibitors, suggested that
this treatment dramatically reduced the chondritis. Serum
levels of Th1 cytokines (interferon-gamma, interleukin-12
[IL-12], and IL-2) paralleled changes in uTIINE levels,
while those of Th2 cytokines (IL-4, IL-5, IL-6, and IL-10)
showed little or no association with disease state or uTIINE
levels. These results indicate that RP might be a
Th1-mediated disease process. Moreover, the uTIINE assay
appears to provide an objective measure of the severity of
chondritis that could assist clinical decisions regarding
adjustments of steroid and other immunosuppressive therapy.
This outcome measure merits investigation in a broader
spectrum of RP patients.},
Key = {fds87707}
}
@article{fds87661,
Author = {TV Stabler and VB Kraus},
Title = {Ascorbic acid accumulates in cartilage in
vivo.},
Journal = {Clinica chimica acta; international journal of clinical
chemistry, Netherlands},
Volume = {334},
Number = {1-2},
Pages = {157-62},
Year = {2003},
Month = {August},
ISSN = {0009-8981},
Keywords = {Adrenal Glands • Animals • Ascorbic Acid •
Cartilage • DNA • Guinea Pigs • Liver •
Male • Oxidation-Reduction • Synovial Fluid •
blood • chemistry • metabolism • metabolism*
• pharmacokinetics*},
Abstract = {BACKGROUND: Ascorbic acid plays an important role in
collagen synthesis. Though ascorbic acid concentrations in
many tissues and in plasma have been characterized, little
is known about in vivo levels in cartilage. MATERIALS AND
METHODS: To discern the role of ascorbic acid in cartilage,
we conducted a dose-response study measuring ascorbic acid
levels in various guinea pig tissues and fluids in response
to this vitamin. To our knowledge, this is the first such
study in cartilage. RESULTS: Ascorbic acid was higher in
synovial fluid compared to paired plasma, and higher in
cartilage than paired synovial fluid. Tissue levels were
normalized to DNA to compare ascorbic acid concentrations
relative to a measure of tissue cellularity. Normalized
cartilage ascorbic acid concentrations were intermediate
between liver (lowest) and adrenal (highest), two well-known
concentrators of ascorbic acid. All tissues and fluids
showed a saturation-effect characterized by large
differences in ascorbic acid concentrations between low- and
medium-dose groups and smaller concentration differences
between medium- and high-dose groups. CONCLUSIONS:
Cartilage, a tissue dependent on ascorbic acid for
extracellular matrix production of collagen, concentrates
ascorbic acid. This concentrating ability is consistent with
the chondrocyte expression of SVCT2, a sodium-dependent
ascorbic acid transporter.},
Key = {fds87661}
}
@article{fds87690,
Author = {RJ Lamers and J DeGroot and EJ Spies-Faber and RH Jellema and VB Kraus and N Verzijl and JM TeKoppele and GK Spijksma and JT Vogels and J van der
Greef, JH van Nesselrooij},
Title = {Identification of disease- and nutrient-related metabolic
fingerprints in osteoarthritic Guinea pigs.},
Journal = {The Journal of nutrition, United States},
Volume = {133},
Number = {6},
Pages = {1776-80},
Year = {2003},
Month = {June},
ISSN = {0022-3166},
Keywords = {Animal Nutrition Physiology* • Animals • Ascorbic
Acid • Diet • Dose-Response Relationship, Drug
• Energy Metabolism • Guinea Pigs • Magnetic
Resonance Spectroscopy • Male • Multivariate
Analysis • Osteoarthritis • Peptide Mapping*
• Purines • Treatment Outcome •
administration & dosage • diagnosis • metabolism
• urine*},
Abstract = {Osteoarthritis (OA), one of the most common diseases among
the elderly, is characterized by the progressive destruction
of joint tissues. Its etiology is largely unclear and no
effective disease-modifying treatment is currently
available. Metabolic fingerprinting provides a novel tool
for the identification of biomarkers. A metabolic
fingerprint consists of a typical combination of metabolites
in a biological fluid and is identified by a combination of
(1)H NMR spectroscopy and multivariate data analysis (MVDA).
The current feasibility study was aimed at identifying a
metabolic fingerprint for OA and applying this in a
nutritional intervention study. Urine samples were collected
from osteoarthritic male Hartley guinea pigs (n = 44) at 10
and 12 mo of age, treated from 4 mo onward with variable
vitamin C doses (2.5-3, 30 and 150 mg/d) and from healthy
male Strain 13 guinea pigs (n = 8) at 12 mo of age, treated
with 30 mg vitamin C/d. NMR measurements were performed on
all urine samples. Subsequently, MVDA was carried out on the
data obtained using NMR. An NMR fingerprint was identified
that reflected the osteoarthritic changes in guinea pigs.
The metabolites that comprised the fingerprint indicate that
energy and purine metabolism are of major importance in OA.
Metabolic fingerprinting also allowed detection of
differences in OA-specific metabolites induced by different
dietary vitamin C intakes. This study demonstrates the
feasibility of metabolic fingerprinting to identify
disease-specific profiles of urinary metabolites. NMR
fingerprinting is a promising means of identifying new
disease markers and of gaining fresh insights into the
pathophysiology of disease.},
Key = {fds87690}
}
@article{fds87695,
Author = {VB Kraus},
Title = {Cyclooxygenase-2 inhibitors and nonsteroidal
anti-inflammatory drugs in the management of
arthritis.},
Journal = {Foot and ankle clinics, United States},
Volume = {8},
Number = {2},
Pages = {187-200, vii},
Year = {2003},
Month = {June},
ISSN = {1083-7515},
Keywords = {Anti-Inflammatory Agents, Non-Steroidal • Arthritis
• Cyclooxygenase Inhibitors • Humans • Joints
• drug effects • drug therapy* • pharmacology
• therapeutic use*},
Abstract = {The management of arthritis pain should be individualized to
the needs and characteristics of the patient. The decision
to use nonsteroidal anti-inflammatory drugs (NSAIDs), and in
particular the cyclooxygenase-2 (COX-2) inhibitors, is
multidimensional. The challenge is to achieve optimal pain
relief at the minimum dose to minimize adverse effects.
Whenever possible, NSAIDs should be given as monotherapies
or in combinations at the lowest effective doses. The COX-2
inhibitors are a safe choice for most patients who are at
low risk for a cardiovascular event. Individuals who are at
risk for thromboses should not receive unopposed COX-2
inhibitors; COX-2 should be given in combination with
low-dose aspirin which is expected to be cardioprotective in
high-risk patients.},
Key = {fds87695}
}
@article{fds87658,
Author = {JM Jordan and G Luta and T Stabler and JB Renner and AD Dragomir and V
Vilim, MC Hochberg and CG Helmick and VB Kraus},
Title = {Ethnic and sex differences in serum levels of cartilage
oligomeric matrix protein: the Johnston County
Osteoarthritis Project.},
Journal = {Arthritis and rheumatism, United States},
Volume = {48},
Number = {3},
Pages = {675-81},
Year = {2003},
Month = {March},
ISSN = {0004-3591},
Keywords = {African Americans • Aged • Biological Markers
• Cartilage, Articular* • Ethnic Groups* •
European Continental Ancestry Group • Extracellular
Matrix Proteins* • Female • Glycoproteins* •
Humans • Knee Joint • Male • Middle Aged
• North Carolina • Osteoarthritis, Knee •
Random Allocation • Rural Health • Rural
Population • Sex Factors* • blood • ethnology
• ethnology* • pathology •
radiography},
Abstract = {OBJECTIVE: Previous descriptions of potential biomarkers of
osteoarthritis (OA) have been limited to Caucasians. In the
present study, we examined associations between serum levels
of cartilage oligomeric matrix protein (COMP) and ethnicity
(African American or Caucasian) and sex in the Johnston
County Osteoarthritis Project, a population-based study of
OA in rural North Carolina. METHODS: All African Americans
and a randomly selected sample of Caucasians who had
available sera and either no radiographic evidence of knee
or hip OA according to the Kellgren/Lawrence (K/L) system
(K/L grade 0) or radiographic evidence of knee OA (K/L grade
2 or higher) were included. Serum COMP levels were
quantified by sandwich enzyme-linked immunosorbent assay,
using monoclonal antibodies 16-F12 and 17-C10. Linear
regression models were used to assess relationships between
serum levels of natural log-transformed COMP (ln COMP) and
ethnicity and sex, controlling for age, height, body mass
index (BMI), radiographic OA, and the presence of other
symptomatic joints. Radiographic OA was defined in separate
models as the presence, severity, and laterality of
radiographic knee OA, the co-occurrence of radiographic knee
and hip OA, and the number of knees and hips with
radiographic OA. RESULTS: The 769 subjects in the study
sample had a mean +/- SD age of 62 +/- 10.3 years. Levels of
ln COMP were associated with age, BMI, and all definitions
of radiographic OA (P = 0.0001), and varied by ethnicity and
sex. In adjusted models, ln COMP was higher in African
American women than in Caucasian women (P = 0.003) and
higher in Caucasian men than Caucasian women (P = 0.0001).
There were no statistically significant differences in serum
ln COMP levels between African American men and women.
CONCLUSION: Serum COMP levels vary by ethnicity and sex.
These factors should be considered in the derivation of
standards using this, and possibly other, potential
biomarkers of OA.},
Key = {fds87658}
}
@article{fds87687,
Author = {V Vilím and Z Vobůrka and R Vytásek and L Senolt and I Tchetverikov and VB Kraus and K Pavelka},
Title = {Monoclonal antibodies to human cartilage oligomeric matrix
protein: epitope mapping and characterization of sandwich
ELISA.},
Journal = {Clinica chimica acta; international journal of clinical
chemistry, Netherlands},
Volume = {328},
Number = {1-2},
Pages = {59-69},
Year = {2003},
Month = {February},
ISSN = {0009-8981},
Keywords = {Antibodies, Monoclonal • Enzyme-Linked Immunosorbent
Assay • Epitope Mapping • Extracellular Matrix
Proteins • Glycoproteins • Humans • Synovial
Fluid • analysis • chemistry • immunology*
• methods*},
Abstract = {BACKGROUND: Cartilage oligomeric matrix protein/thrombospondin
5 (COMP/TSP 5) is one of the most promising serologic
markers with regard to an ability to prognose development of
osteoarthritis (OA). Our aim was to map the epitopes of
three monoclonal antibodies (mAb) to COMP and to develop and
characterize a sandwich enzyme-linked immunosorbent assay
(ELISA) for measuring COMP levels in human body fluids.
METHODS: COMP was digested with trypsin and the
NH(2)-terminal sequence of the fragments recognized by each
of the mAbs was determined. Steric competition among the
mAbs was tested with an antibody capture assay. A sandwich
ELISA was developed using unlabeled mAb 16-F12 as a capture
antibody, and mAb 17-C10 labeled with biotin as the second
antibody. RESULTS: Epitopes of the three mAbs were mapped to
three different domains within the COMP subunit (16-F12,
NH(2)-terminal domain; 17-C10, EGF-like domain; 12-C4,
COOH-terminal domain). These epitopes did not overlap. mAbs
17-C10 and 12-C4 yielded similar serum COMP results when
used as the secondary antibodies. Serum COMP levels measured
with the new sandwich ELISA using mAbs 16-F12 and 17-C10
correlated strongly with results based on an inhibition
ELISA with mAb 17-C10 alone (r(2) = 0.836; P < 0.0001). We
characterized the new sandwich ELISA with regards to inter-
and intra-assay variability, the range of COMP levels that
can be expected in human synovial fluids (SF) and sera
(controls and OA and rheumatoid arthritis (RA) patients),
and the day-to-day and diurnal variability of COMP levels in
sera. CONCLUSIONS: We have developed and characterized a
sandwich ELISA for COMP that is sensitive and yields highly
reproducible COMP results upon analysis of human sera and
synovial fluids.},
Key = {fds87687}
}
@article{fds87709,
Author = {JL Huebner and MA Hanes and B Beekman and JM TeKoppele and VB
Kraus},
Title = {A comparative analysis of bone and cartilage metabolism in
two strains of guinea-pig with varying degrees of naturally
occurring osteoarthritis.},
Journal = {Osteoarthritis and cartilage / OARS, Osteoarthritis Research
Society},
Volume = {10},
Number = {10},
Pages = {758-67},
Year = {2002},
Month = {October},
ISSN = {1063-4584},
Keywords = {Amino Acids • Animals • Bone Density • Bone
and Bones • Cartilage, Articular • Guinea Pigs
• Hindlimb • Joints • Keratan Sulfate •
Male • Microscopy, Electron • Osteoarthritis
• Osteocalcin • Pilot Projects • Synovial
Fluid • analysis • blood • metabolism •
metabolism* • pathology • urine},
Abstract = {OBJECTIVE: To evaluate the interaction of bone and cartilage
in knee osteoarthritis (OA) pathogenesis in two guinea-pig
strains with appreciable differences in bone metabolism.
METHODS: Two guinea-pig strains were evaluated for their
susceptibilities to OA using semi-quantitative histological
grading of knee joints and quantification of biomarkers
including urinary excretion of hydroxylysyl-pyridinoline
(HP) and lysyl-pyridinoline (LP) collagen cross-links, serum
osteocalcin (OC), and synovial fluid levels of keratan
sulfate (KS). RESULTS: At 12 months of age, Strain 13
guinea-pigs had minimal to mild histological evidence of OA
compared to the Hartley strain guinea-pigs. The Hartley
strain, with more severe OA, had a higher rate of bone
formation (serum osteocalcin) and bone resorption (HP and
LP) evident at a young age with persistence of a greater
rate of bone formation at 12 months of age. The Strain 13
possessed much thicker subchondral bone at the outset (2
months) compared to the Hartley; however, the Hartley strain
showed the greatest increase in subchondral bone thickness
coincident with the development of cartilage degeneration.
Thus, the process of subchondral bone thickening, in
contrast to the absolute initial subchondral bone thickness,
was a hallmark of OA in the guinea-pig. Moreover, Strain 13
had lower intraarticular proteoglycan turnover. Levels of
synovial fluid keratan sulfate were positively correlated
with the severity of histological OA. CONCLUSIONS: This
pilot study represents the first evidence of differential
susceptibility to OA in guinea-pigs. Comparison of these two
strains of guinea-pig has revealed that increased metabolism
within the affected tissues, cartilage and bone, is
associated with the development and progression of OA. This
work demonstrates that the Strain 13 is a viable age-matched
control to the Hartley strain and merits a more in depth
evaluation of the contribution of bone and bone metabolism
to OA.},
Language = {eng},
Key = {fds87709}
}
@article{fds87693,
Author = {CM Flahiff and DA Narmoneva and JL Huebner and VB Kraus and F Guilak and LA
Setton},
Title = {Osmotic loading to determine the intrinsic material
properties of guinea pig knee cartilage.},
Journal = {Journal of biomechanics, United States},
Volume = {35},
Number = {9},
Pages = {1285-90},
Year = {2002},
Month = {September},
ISSN = {0021-9290},
Keywords = {Animals • Cartilage, Articular • Elasticity •
Femur • Guinea Pigs • Knee Joint • Male
• Microscopy, Confocal • Microscopy, Fluorescence
• Osmotic Pressure • Patella •
Reproducibility of Results • Sensitivity and
Specificity • Stress, Mechanical • Tibia •
cytology* • methods • physiology •
physiology*},
Abstract = {Few methods exist to study cartilage mechanics in small
animal joints due to the difficulties associated with
handling small tissue samples. In this study, we apply an
osmotic loading method to quantify the intrinsic material
properties of articular cartilage in small animal joints.
Cartilage samples were studied from the femoral condyle and
tibial plateau of two-month old guinea pigs. Swelling
strains were measured using confocal fluorescence scanning
microscopy in samples subjected to osmotic loading. A
histochemical staining method was developed and calibrated
for quantification of negative fixed charge density in
guinea pig cartilage. Site-matched swelling strain data and
fixed charge density values were then used with a triphasic
theoretical model for cartilage swelling to determine the
uniaxial modulus of the cartilage solid matrix. Moduli
obtained in this study (7.2 MPa femoral condyle; 10.8 MPa,
tibial plateau) compare well with previously reported values
for the tensile moduli of human and other animal cartilages
determined from uniaxial tension experiments. This study
provides the first available data for material properties
and fixed charge density in cartilage from the guinea pig
knee and suggests a promising method for tracking changes in
cartilage mechanics in small animal models of
degeneration.},
Key = {fds87693}
}
@article{fds87699,
Author = {AD Dragomir and VB Kraus and JB Renner and G Luta and A Clark and V Vilim and MC Hochberg and CG Helmick and JM Jordan},
Title = {Serum cartilage oligomeric matrix protein and clinical signs
and symptoms of potential pre-radiographic hip and knee
pathology.},
Journal = {Osteoarthritis and cartilage / OARS, Osteoarthritis Research
Society, England},
Volume = {10},
Number = {9},
Pages = {687-91},
Year = {2002},
Month = {September},
ISSN = {1063-4584},
Keywords = {Aged • Aged, 80 and over • Cartilage, Articular
• Enzyme-Linked Immunosorbent Assay •
Extracellular Matrix Proteins • Female •
Glycoproteins • Hip Joint • Humans • Knee
Joint • Male • Middle Aged • blood* •
pathology • pathology* • radiography},
Abstract = {OBJECTIVE: To examine the cross-sectional relationship
between serum cartilage oligomeric matrix protein (COMP) and
hip and knee clinical signs and symptoms in a sample of
adults without radiographic hip or knee osteoarthritis (OA).
DESIGN: A total of 145 persons with available sera and no
evidence of radiographic hip or knee OA (Kellgren-Lawrence
grade 0) were randomly selected from the Caucasian
participants of the Johnston County Osteoarthritis Project.
COMP was quantified by a competitive ELISA assay with a
monoclonal antibody 17-C10. Hip and knee clinical signs and
symptoms were assessed by physical examination and
interview, and their associations with Ln COMP analysed with
general linear models. RESULTS: After adjustment for age,
gender, body mass index (BMI), and other symptomatic joints,
mean Ln COMP was statistically significantly higher among
persons with hip-related clinical signs (P=0.018), among
those with hip-related symptoms (P=0.046), and among
individuals meeting American College of Rheumatology
clinical criteria for hip OA (P=0.021). There were no
statistically significant associations between any of the
knee-related clinical signs and symptoms and Ln COMP.
CONCLUSION: Serum COMP may be useful as a biomarker of
pre-radiographic hip joint pathology; its utility as a
biomarker of pre-radiographic knee joint pathology is
unclear.},
Key = {fds87699}
}
@article{fds87700,
Author = {V Vilím and M Olejárová and S Machácek and J Gatterová and VB
Kraus, K Pavelka},
Title = {Serum levels of cartilage oligomeric matrix protein (COMP)
correlate with radiographic progression of knee
osteoarthritis.},
Journal = {Osteoarthritis and cartilage / OARS, Osteoarthritis Research
Society, England},
Volume = {10},
Number = {9},
Pages = {707-13},
Year = {2002},
Month = {September},
ISSN = {1063-4584},
Keywords = {Aged • Cartilage, Articular • Double-Blind Method
• Enzyme-Linked Immunosorbent Assay •
Extracellular Matrix Proteins • Female •
Glycoproteins • Humans • Knee Joint • Male
• Middle Aged • Osteoarthritis, Knee •
Prospective Studies • blood • blood* •
pathology • radiography • radiography*},
Abstract = {OBJECTIVE: To evaluate the prognostic utility of serum COMP
level measured with a new sandwich ELISA, by correlating
COMP level with outcome measures of osteoarthritis (OA)
progression. DESIGN: Patients (N=48) had symptomatic primary
knee OA of Kellgren-Lawrence (K-L) grade I-III and met ACR
criteria. These patients were evaluated prospectively as
part of a double-blind drug trial of 3 years' duration and
represented the placebo arm of the study. Serum COMP levels
were measured by sandwich ELISA with monoclonal antibodies
16-F12 and 17-C10 at baseline and at study end and levels
were correlated with changes in (1) joint space width (JSW),
(2) K-L grade, (3) Lequesne, and (4) WOMAC indices, over 3
years. RESULTS: The change in JSW over 3 years, summed for
both knees, correlated positively with serum COMP level at
baseline as well as at study end. Patients were sorted by
level of progression based upon a change in K-L grade summed
for both knees over 3 years; patients who progressed by two
K-L grades were shown to have had significantly higher COMP
levels at baseline as well as at study end. Baseline and
study end COMP levels did not correlate with the change of
Lequesne or WOMAC indices. Baseline COMP levels correlated
strongly with end serum COMP levels. CONCLUSION: Serum COMP
has the potential to be a prognostic marker of disease
progression. High COMP levels, persisting over the 3-year
study period in the patients with radiographic progression,
indicated differences in disease activity detectable
throughout the entire follow-up interval.},
Key = {fds87700}
}
@article{fds87697,
Author = {C Fink and HJ Cooper and JL Huebner and F Guilak and VB
Kraus},
Title = {Precision and accuracy of a transportable dual-energy X-ray
absorptiometry unit for bone mineral measurements in guinea
pigs.},
Journal = {Calcified tissue international, United States},
Volume = {70},
Number = {3},
Pages = {164-9},
Year = {2002},
Month = {March},
ISSN = {0171-967X},
Keywords = {Animals • Bone Density • Densitometry, X-Ray
• Guinea Pigs • Male • Observer Variation
• Quality Control • Reproducibility of Results
• Statistics • methods* •
physiology*},
Abstract = {Dual energy X-ray absorptiometry (DXA) is a valuable tool
for measuring bone mineral content (BMC) and bone mineral
density (BMD) in small-animal research. The present study
was devised to establish guidelines and to define sites for
bone mineral measurements in guinea pigs and to evaluate the
accuracy of a new transportable research DXA unit. Repeated
scans were performed on 30 guinea pig hindlimbs (in situ) as
well as the isolated bones from these limbs (ex situ). Nine
exactly specified regions of interest (ROIs) were analyzed
twice for BMC and BMD by three different observers.
Additionally, the BMC of whole bones and bone segments as
measured by DXA was correlated to ash weights of bone in a
subset of five animals to determine the accuracy of the DXA
measurements. On ex situ scans, intra-observer variability
for BMD ranged from 0.09% to 2.33% and inter-observer
variability from 0.23% to 5.86% depending on the site
studied, with smaller ROIs exhibiting more variability.
Coefficients of variance (CV) for BMC measurements were
slightly higher than for BMD. However, BMC offered a better
correlation between in situ and ex situ values than BMD. On
in situ scans, observer variability for BMD and BMC for
comparable sites was higher than the ex situ variability.
The results of this study indicate that DXA provides an
accurate measurement of BMC even in small specimens. The
precision of BMC and BMD measurements in situ can be
improved considerably by using specific, well-defined ROIs
and by careful placement of the bones to be scanned in close
proximity to the scanning surface.},
Key = {fds87697}
}
@article{fds87708,
Author = {AG Clark and AL Rohrbaugh and I Otterness and VB Kraus},
Title = {The effects of ascorbic acid on cartilage metabolism in
guinea pig articular cartilage explants.},
Journal = {Matrix biology : journal of the International Society for
Matrix Biology},
Volume = {21},
Number = {2},
Pages = {175-84},
Year = {2002},
Month = {March},
ISSN = {0945-053X},
Keywords = {Aggrecans • Animals • Ascorbic Acid •
Cartilage, Articular • Cloning, Molecular •
Collagen • Collagen Type II • Culture Techniques
• Extracellular Matrix • Extracellular Matrix
Proteins* • Gene Expression • Guinea Pigs •
Lectins, C-Type • Male • Organic Anion
Transporters, Sodium-Dependent • Procollagen-Proline
Dioxygenase • Protein Biosynthesis • Proteins
• Proteoglycans • RNA • Sodium-Coupled
Vitamin C Transporters • Symporters* •
Transcription, Genetic • biosynthesis • drug
effects* • genetics • genetics* • metabolism
• pharmacology*},
Abstract = {Ascorbic acid has been associated with the slowing of
osteoarthritis progression in guinea pig and man. The goal
of this study was to evaluate transcriptional and
translational regulation of cartilage matrix components by
ascorbic acid. Guinea pig articular cartilage explants were
grown in the presence of L-ascorbic acid (L-Asc),
D-isoascorbic acid (D-Asc), sodium L-ascorbate (Na L-Asc),
sodium D-isoascorbate (Na D-Asc), or ascorbyl-2-phosphate
(A2P) to isolate and analyze the acidic and nutrient effects
of ascorbic acid. Transcription of type II collagen, prolyl
4-hydroxylase (alpha subunit), and aggrecan increased in
response to the antiscorbutic forms of ascorbic acid (L-Asc,
Na L-Asc, and A2P) and was stereospecific to the L-forms.
Collagen and aggrecan synthesis also increased in response
to the antiscorbutic forms but only in the absence of
acidity. All ascorbic acid forms tended to increase
oxidative damage over control. This was especially true for
the non-nutrient D-forms and the high dose L-Asc. Finally,
we investigated the ability of chondrocytes to express the
newly described sodium-dependent vitamin C transporters
(SVCTs). We identified transcripts for SVCT2 but not SVCT1
in guinea pig cartilage explants. This represents the first
characterization of SVCTs in chondrocytes. This study
confirms that ascorbic acid stimulates collagen synthesis
and in addition modestly stimulates aggrecan synthesis.
These effects are exerted at both transcriptional and
post-transcriptional levels. The stereospecificity of these
effects is consistent with chondrocyte expression of SVCT2,
shown previously to transport L-Asc more efficiently than
D-Asc. Therefore, this transporter may be the primary
mechanism by which the L-forms of ascorbic acid enter the
chondrocyte to control matrix gene activity.},
Language = {eng},
Key = {fds87708}
}
@article{fds87660,
Author = {VB Kraus and JL Huebner and C Fink and JB King and S Brown and TP Vail and F
Guilak},
Title = {Urea as a passive transport marker for arthritis biomarker
studies.},
Journal = {Arthritis and rheumatism},
Volume = {46},
Number = {2},
Pages = {420-7},
Year = {2002},
Month = {February},
ISSN = {0004-3591},
Keywords = {Animals • Arthritis • Biological Markers •
Biological Transport • Cartilage • Chymopapain
• Dogs • Extracellular Matrix Proteins •
Glucose • Glycoproteins • Joints • Keratan
Sulfate • Lactic Acid • Osmolar Concentration
• Synovial Fluid • Urea • analysis •
chemically induced • chemistry • metabolism •
metabolism* • physiology},
Abstract = {OBJECTIVE: To develop a method to correct for the unknown
dilution of synovial fluid that occurs during lavage of a
joint, we evaluated the utility of urea, a molecule that is
neither synthesized nor metabolized by joint tissues, as a
means of correcting for the dilutional effects of lavage
procedures and effusions. METHODS: Joint fluids were
obtained from normal canine joints by direct aspiration (n =
41) and lavage (n = 10). Acute joint injury was induced in 4
joints by intraarticular injection of chymopapain. Serum and
joint fluid levels of urea and joint fluid concentrations of
glucose, lactate, cartilage oligomeric matrix protein
(COMP), and keratan sulfate (KS) were measured in these 55
joints. RESULTS: Urea concentrations in joint fluid were
directly proportional to those in serum throughout a wide
range of concentrations in normal joints. From this
relationship, the dilution factor introduced by joint lavage
was determined. This method was applied to quantify
biomarker concentrations in synovial lavage fluid and was
found to successfully correct for lavage-induced dilution of
glucose, lactate, COMP, and KS to levels equivalent to those
in samples aspirated directly. In the context of
chymopapain-induced joint effusion, urea concentrations
continued to be proportional to serum concentrations, but
were much lower, enabling an estimation of the change in the
volume of distribution (V(d)) of a marker due to a change in
joint water content in the setting of inflammation
characterized by effusion. Lactate and KS levels rose
markedly in response to chymopapain. After adjustment for
the V(d), the glucose concentration in the
chymopapain-injected joints did not change. CONCLUSIONS:
Urea provides a robust method of quantifying and correcting
for the dilution of synovial fluid due to joint lavage or
inflammation. This method is potentially applicable to
surrogate marker studies in human arthritis.},
Language = {eng},
Key = {fds87660}
}
@article{fds87662,
Author = {CS Carlson and F Guilak and TP Vail and JF Gardin and VB
Kraus},
Title = {Synovial fluid biomarker levels predict articular cartilage
damage following complete medial meniscectomy in the canine
knee.},
Journal = {Journal of orthopaedic research : official publication of
the Orthopaedic Research Society, United
States},
Volume = {20},
Number = {1},
Pages = {92-100},
Year = {2002},
Month = {January},
ISSN = {0736-0266},
Keywords = {Animals • Biological Markers • Cartilage,
Articular • Dogs • Knee Joint • Menisci,
Tibial • Predictive Value of Tests • Synovial
Fluid • Tibia • chemistry* • pathology •
pathology* • surgery • surgery*},
Abstract = {The purposes of this study were to document the histological
changes present in the tibial plateaus 12 weeks after
complete medial meniscectomy in dogs and to determine if
synovial lavage fluid biomarker levels are predictive of the
severity of joint damage. Twelve adult dogs underwent
complete unilateral medial meniscectomy and synovial lavage
fluid biomarker levels, including cartilage oligomeric
matrix protein (COMP), keratan sulfate (5D4). 3B3(-), and
3B3(+), were measured serially at 4-week intervals. The dogs
were euthanized 12 weeks after surgery and each medial and
lateral tibial plateau from the meniscectomized and
contralateral knees was graded histologically. Histological
data were analyzed using principal components analysis,
which resulted in 4 factors that explained 70% of the
variation in the data. Factor 2 (weighted most heavily by
subchondral bone thickness) and Factor 3 (representative of
articular cartilage damage) were significantly affected by
compartmental site (P < 0.01 for both). Both of these
factors were highest in the medial tibial plateau of the
meniscectomized knee, and Factor 3 was significantly higher
in this site than in the medial tibial plateau of the
contralateral knee (P < 0.01). Peak levels of all 4 synovial
lavage fluid biomarkers occurred at 4 weeks
post-meniscectomy and 4-week minus baseline levels of all
biomarkers were significantly correlated with the Factor 3
scores. This study demonstrates that significant articular
cartilage damage occurs relatively quickly following
complete medial meniscectomy in dogs and establishes the
content and criterion validity for these synovial fluid
lavage biomarkers in canine meniscectomy as surrogate
measures of articular cartilage damage.},
Key = {fds87662}
}
@article{fds87711,
Author = {V Vilím and R Vytásek and M Olejárová and S Machácek and J
Gatterová, B Procházka and VB Kraus and K Pavelka},
Title = {Serum cartilage oligomeric matrix protein reflects the
presence of clinically diagnosed synovitis in patients with
knee osteoarthritis.},
Journal = {Osteoarthritis and cartilage / OARS, Osteoarthritis Research
Society, England},
Volume = {9},
Number = {7},
Pages = {612-8},
Year = {2001},
Month = {October},
ISSN = {1063-4584},
Keywords = {Adult • Age Factors • Aged • Analysis of
Variance • Antibodies, Monoclonal • Biological
Markers • C-Reactive Protein • Confidence
Intervals • Enzyme-Linked Immunosorbent Assay •
Extracellular Matrix Proteins • Female •
Glycoproteins • Humans • Linear Models • Male
• Middle Aged • Normal Distribution •
Osteoarthritis, Knee • Sensitivity and Specificity
• Severity of Illness Index • Statistics,
Nonparametric • Synovitis • analysis • blood
• blood* • complications • diagnostic use
• etiology • methods},
Abstract = {OBJECTIVE: Cartilage oligomeric matrix protein (COMP) is a
component of articular cartilage whose serum levels show a
strong correlation with radiographic osteoarthritis (OA)
status. It has recently been found, however, that COMP is
also produced in synovium. To assess the hypothesis that
synovitis affects serum COMP levels in patients with knee
OA, we collected sera for COMP simultaneous with a clinical
examination for synovitis. DESIGN: Sera were collected from
OA patients who fulfilled the American College of
Rheumatology criteria for knee OA. Radiographs were
classified according to the grading system of Kellgren and
Lawrence. Synovitis was diagnosed clinically by joint
tenderness plus swelling and/or increased warmth over the
joint. COMP levels in sera were measured by inhibition ELISA
with monoclonal antibody (mAb) 17-C10. RESULTS: Serum COMP
levels were significantly correlated with age, synovitis and
an interaction of synovitis and OA severity. Synovitis
showed the strongest effect on COMP levels (R=0.1587, P<
0.01), in contrast to C-reactive protein, duration of OA and
OA severity score which showed no significant effect on COMP
levels. Individual signs of synovitis, namely, joint
tenderness and warmth had a significant effect on serum COMP
levels while swelling alone did not. CONCLUSION: Synovitis
exerts a significant effect on serum COMP levels measured
with mAb 17-C10 in OA patients. These findings underscore
the importance of the clinical joint examination to assess
for synovitis, when attempting to apply objective measures,
such as COMP, to the clinical setting.},
Key = {fds87711}
}
@article{fds87702,
Author = {JY Wang and AE Baer and VB Kraus and LA Setton},
Title = {Intervertebral disc cells exhibit differences in gene
expression in alginate and monolayer culture.},
Journal = {Spine, United States},
Volume = {26},
Number = {16},
Pages = {1747-51; discussion 1752},
Year = {2001},
Month = {August},
ISSN = {0362-2436},
Keywords = {Aggrecans • Alginates • Animals • Cells,
Cultured • Collagen • Culture Media • Culture
Techniques • DNA Primers • Extracellular Matrix
Proteins* • Gene Expression • Glucuronic Acid
• Hexuronic Acids • Intervertebral Disk •
Lectins, C-Type • Lumbar Vertebrae • Phenotype
• Proteoglycans • RNA, Messenger • Reverse
Transcriptase Polymerase Chain Reaction • Swine •
biosynthesis • chemistry • cytology • drug
effects* • genetics* • metabolism • methods*
• pharmacology*},
Abstract = {STUDY DESIGN: The mRNA levels of aggrecan and collagen were
quantified in intervertebral disc cells cultured under three
conditions: primary alginate culture, monolayer culture, and
re-encapsulation in alginate after monolayer culture.
OBJECTIVES: To compare the phenotype of intervertebral disc
cells under different culture conditions and to investigate
the reversibility of cell phenotype after re-encapsulation
in alginate after monolayer culture. SUMMARY OF BACKGROUND
DATA: The intervertebral disc contains heterogeneous
populations of cells that vary with anatomic region. These
cells possess significant differences in phenotype that can
be preserved in vitro, although the effect of culture
conditions on the phenotype of these cells is poorly
understood. METHODS: The intervertebral disc cells of
4-5-month-old pigs were isolated enzymatically from three
anatomic zones: anulus fibrosus (AF), transition zone (TZ),
and nucleus pulposus (NP). Gene expression levels of
aggrecan and collagen Types I and II were measured using a
quantitative reverse transcriptase--polymerase chain
reaction. RESULTS: Gene expression levels of anulus fibrosus
and transition zone cells were shifted in monolayer compared
with alginate, although the shift was partially reversed
when re-encapsulated in alginate. However, NP cells appeared
to be insensitive to culture conditions. Furthermore,
characteristic patterns of gene expression among AF, TZ, and
NP cells in primary alginate culture did not exist in
monolayer culture, but they were also observed after
re-encapsulation in alginate. CONCLUSION: The findings of
this study suggest that anulus fibrosus and transition zone
cells undergo a reversible shift in phenotype when cultured
in monolayer compared with alginate. These differences
suggest that the culture system exerts a strong influence on
cell phenotype and may play a role in the response of these
cells to biophysical and biochemical stimuli in
vitro.},
Key = {fds87702}
}
@article{fds87698,
Author = {EW St Clair and WE Wilkinson and DS Pisetsky and DJ Sexton and R Drew and VB Kraus and RA Greenwald},
Title = {The effects of intravenous doxycycline therapy for
rheumatoid arthritis: a randomized, double-blind,
placebo-controlled trial.},
Journal = {Arthritis and rheumatism, United States},
Volume = {44},
Number = {5},
Pages = {1043-7},
Year = {2001},
Month = {May},
ISSN = {0004-3591},
Keywords = {Adult • Amino Acids • Anti-Bacterial Agents •
Arthritis, Rheumatoid • Azithromycin • Collagen
• Double-Blind Method • Doxycycline • Female
• Humans • Injections, Intravenous • Male
• Middle Aged • Patient Dropouts •
administration & dosage • administration & dosage*
• adverse effects • drug therapy* •
metabolism • urine},
Abstract = {OBJECTIVE: To determine the feasibility, safety, and
potential clinical efficacy of intravenous (IV) doxycycline
therapy for rheumatoid arthritis (RA), as well as its
possible effects on serum and urinary markers of collagen
breakdown. METHODS: The exploratory trial was designed as a
16-week, single-center, randomized, double-blind,
placebo-controlled trial. Eligible subjects with active
seropositive or erosive RA were randomly allocated into 3
treatment groups: doxycycline 200 mg IV, azithromycin 250 mg
orally, or placebo. The blinded IV study drug was
administered once daily for the first 3 weeks by home
self-infusion and then weekly for the next 8 weeks,
concurrent with the blinded oral study drug at the
prescribed doses. The primary end points were the change
between baseline and week 4 in the tender joint count,
erythrocyte sedimentation rate, and urinary excretion of
pyridinoline. RESULTS: The trial was stopped prematurely
after enrollment of 31 patients. Three subjects were
withdrawn because of worsening arthritis, and 1 patient was
withdrawn when newly diagnosed with breast cancer.
Infusion-related events occurred in 13 (42%) of 31 patients,
but none were serious. There were 4 serious adverse events
unrelated to the study drug, including a new diagnosis of
breast cancer in 3 cases and hospitalization for abdominal
pain in 1 case. No significant differences were observed
across treatment groups in any of the 3 primary clinical end
points. CONCLUSION: Although IV doxycycline therapy was
generally well-tolerated by patients in this trial, it did
not show any evidence of reducing disease activity or
collagen crosslink production.},
Key = {fds87698}
}
@article{fds87692,
Author = {AE Baer and JY Wang and VB Kraus and LA Setton},
Title = {Collagen gene expression and mechanical properties of
intervertebral disc cell-alginate cultures.},
Journal = {Journal of orthopaedic research : official publication of
the Orthopaedic Research Society, United
States},
Volume = {19},
Number = {1},
Pages = {2-10},
Year = {2001},
Month = {January},
ISSN = {0736-0266},
Keywords = {Alginates • Animals • Biomechanics • Cells,
Cultured • Collagen • Glucuronic Acid •
Hexuronic Acids • Intervertebral Disk • RNA,
Messenger • Swine • analysis • cytology*
• genetics* • metabolism},
Abstract = {Cells of the intervertebral disc have a limited capacity for
matrix repair that may contribute to the onset and
progression of degenerative disc changes. In this study, the
biosynthetic capacity of cells isolated from specific
regions of the porcine intervertebral disc was evaluated in
vitro. Using a competitive reverse transcription-polymerase
chain reaction technique, gene expression levels for types I
and II collagen were quantified in cells cultured for up to
21 d in a three-dimensional alginate culture system and
compared to levels obtained for cells in vivo. The
mechanical properties of cell-alginate constructs were
measured in compression and shear after periods of culture
up to 16 weeks. Cells from the anulus fibrosus expressed the
most type I collagen mRNA in vivo and in vitro, while cells
from the transition zone expressed the most type II collagen
mRNA in vivo and in vitro. Mechanical testing results
indicate that a mechanically functional matrix did not form
at any time during the culture period; rather, decreases of
up to 50% were observed in the compressive and shear moduli
of the cell-alginate constructs compared to alginate with no
cells. Together with results of prior studies, these results
suggest that intervertebral disc cells maintain
characteristics of their phenotype when cultured in
alginate, but the molecules they synthesize are not able to
form a mechanically functional matrix in
vitro.},
Key = {fds87692}
}
@article{fds87649,
Title = {3. Wang, YJ, AE. Baer, VB Kraus, and LA Setton. 2001.
Intervertebral Disc Cells Exhibit Differences in Gene
Expression in Alginate and Monolayer Culture. Spine 26:
1747-1751.},
Year = {2001},
Key = {fds87649}
}
@article{fds87650,
Title = {6. Kraus, VB, JL Huebner, C Fink, J King, S Brown, TP Vail
and F Guilak. 2001. Urea as a passive transport marker for
arthritis biomarker studies. Arthritis & Rheum (In
Press).},
Year = {2001},
Key = {fds87650}
}
@article{fds87651,
Title = {10. Flahiff, CM, Narmoneva DA, Huebner JL, Kraus VB, Guilak
F and Setton LA. 2001. Osmotic loading to determine the
intrinsic material properties of guinea pig knee cartilage.
J Biomechanics (In Press).},
Year = {2001},
Key = {fds87651}
}
@article{fds87652,
Title = {3. St. Clair, EW and VB Kraus. 2001. The pathophysiology and
treatment of rheumatoid arthritis and osteoarthritis. In The
Pathophysiology and Therapeutics of Human Disease, eds, F
Neelon, in press.},
Year = {2001},
Key = {fds87652}
}
@article{fds87653,
Title = {4. VB Kraus, Y Li, E Martin, JA Jordan, JB Renner, M
Doherty, AG Wilson, R Moskowitz, M Hochberg, R Loeser, Scott
Sundseth. 2001. Articular hypermobility and hand
osteoarthritis. Arthritis Rheum 44 (9 Suppl):
529.},
Year = {2001},
Key = {fds87653}
}
@article{fds87654,
Title = {5. Chen,J; JY Wang; AE Baer, VB Kraus and LA Setton. 2002.
Zone analysis of gene expression in intervertebral disc
tissue by cDNA microarray and real- time quantitative
RT-PCR. Trans Orthop Res Soc 27: 811.},
Year = {2001},
Key = {fds87654}
}
@article{fds87655,
Title = {7. Rohrbaugh, R, A Clark and VB Kraus. 2002 meeting. The
effects of ascorbic acid on cartilage metabolism in
articular cartilage explants. Trans Orthop Res Soc 27:
373.},
Year = {2001},
Key = {fds87655}
}
@article{fds87673,
Title = {1. Baer AE, Wang JY, Kraus VB, Setton LA: Collagen gene
expression and mechanical properties of intervertebral disc
cell-alginate cultures. J Orthop Res 19:2-10,
2001.},
Year = {2001},
Key = {fds87673}
}
@article{fds87674,
Title = {2. Vilim, V, R Vytasek, M Olejarova, S Machasek, J
Gatterova, B Prochazka, VB Kraus, and K Pavelka. 2001. Serum
cartilage oligomeric matrix protein reflects the presence of
clinically diagnosed synovitis in patients with knee
osteoarthritis. Osteoarthritis & Cartilage
9:612-618.},
Year = {2001},
Key = {fds87674}
}
@article{fds87675,
Title = {4. Hale, LP, AG Clark, J Li, PK Greer and VB Kraus. 2001.
Age-related thymic atrophy in the guinea pig: effects of
long-term supplementation with vitamin C. Developmental and
Comparative Immunology 25: 509-518.},
Year = {2001},
Key = {fds87675}
}
@article{fds87676,
Title = {5. St.Clair, WE, WE Wilkinson, DS Pisetsky, DJ Sexton, R
Drew, VB Kraus and RW Greenwald. 2001. Intravenous
doxycycline therapy for rheumatoid arthritis. Arthritis
Rheum 44(5):1043-1047.},
Year = {2001},
Key = {fds87676}
}
@article{fds87677,
Title = {7. Carlson, CS, F Guilak, TP Vail, JF Gardin and VB Kraus.
2001. Synovial fluid biomarker levels predict articular
cartilage damage following complete medial meniscectomy in
the canine knee. J Orthopaedic Res (in press).},
Year = {2001},
Key = {fds87677}
}
@article{fds87678,
Title = {*Guilak, F, LA Setton, and VB Kraus. 2000. Structure and
function of articular cartilage. In Principles and Practice
of Orthopaedic Sports Medicine, eds. WE Garrett Jr., KP
Speer, and DT Kirkendall, Lippincott Williams and Wilkins,
Philadelphia, pp. 53-73.},
Year = {2001},
Key = {fds87678}
}
@article{fds87679,
Title = {2. *Kraus, VB and D Wiggin. Arthritis. 2002. In Textbook of
Clinical Exercise Physiology, eds. J Ehrman, P Gordan, P
Visich and S Keteyian, Human Kinetics, Champaign, IL., in
press.},
Year = {2001},
Key = {fds87679}
}
@article{fds87680,
Title = {4. *Kraus, VB and E Martin. 2002. Laboratory approaches to
the identification of genetic association in osteoarthritis.
In Osteoarthritis (2nd ed), eds, K Brandt, M Doherty and S
Lohmander, Oxford University Press, Oxford, in
press.},
Year = {2001},
Key = {fds87680}
}
@article{fds87681,
Title = {Published Abstracts or Transactions (year 2001) 1. Vilim, V,
S Machacek, L Sedova, J Gatterova, VB Kraus and K Pavelka.
2001. Determination of serum COMP by sandwich ELISA
indicates no prognostic value in early rheumatoid arthriits.
Transactions of the Orthopaedic Research Society (26):
648.},
Year = {2001},
Key = {fds87681}
}
@article{fds87682,
Title = {2. Huguenin, T, JM Jordan, VB Kraus, G Luta, JB Renner, AD
Dragomir, A Salazar, MC Hochberg and CG Helmick. 2001.
Clinical and symptomatic hand osteoarthritis and functional
status. Arthritis Rheum 44 (9 Suppl): 1042.},
Year = {2001},
Key = {fds87682}
}
@article{fds87683,
Title = {3. VB Kraus, G Varju, Y Li, E Martin, JA Jordan, JB Renner,
M Doherty, AG Wilson, R Moskowitz, M Hochberg, R Loeser, S
Sundseth. 2001. Assessment of the usefulness of clinical
hand examination for determination of OA affected status for
genetic studies. Arthritis Rheum 44 (9 Suppl):
528.},
Year = {2001},
Key = {fds87683}
}
@article{fds87684,
Title = {6. Vilim, V, M Olejarova, S Machacek, J Gatterova, VB Kraus
and K Pavelka. 2002 meeting. Serum levels of COMP correlate
with radiographic progression of knee osteoarthritis. Trans
Orthop Res Soc 27: 421.},
Year = {2001},
Key = {fds87684}
}
@article{fds87685,
Author = {E Lindhorst and TP Vail and F Guilak and H Wang and LA Setton and V Vilim and VB Kraus},
Title = {Longitudinal characterization of synovial fluid biomarkers
in the canine meniscectomy model of osteoarthritis.},
Journal = {Journal of orthopaedic research : official publication of
the Orthopaedic Research Society, UNITED
STATES},
Volume = {18},
Number = {2},
Pages = {269-80},
Year = {2000},
Month = {March},
ISSN = {0736-0266},
Keywords = {Animals • Bacterial Proteins • Biological Markers
• Cartilage, Articular • Chondroitin Sulfates
• Disease Models, Animal* • Dogs • Epitopes
• Keratan Sulfate • Male • Membrane Proteins*
• Menisci, Tibial • Osteoarthritis • Synovial
Fluid • Transferases* • analysis* •
chemistry* • metabolism* • pathology •
surgery*},
Abstract = {Damage to the meniscus can lead to posttraumatic
osteoarthritis. Early markers of joint injury and tissue
disease may be useful in developing and administering
clinical treatment. We investigated the effects of total
medial meniscectomy on biomarkers measured serially in
synovial lavage fluid each month for 3 months. Following
meniscectomy in dogs, four biomarkers were evaluated:
cartilage oligomeric matrix protein, keratan sulfate epitope
(5D4), the 3B3(-) neoepitope of chondroitin-6-sulfate, and
the 3B3(+) chondroitinase-generated epitope of
chondroitin-6-sulfate. Meniscectomy led to statistically
significant elevations of all four biomarkers, with levels
peaking at 4 weeks. By 12 weeks, the level of the 5D4
epitope returned to the preoperative baseline level whereas
that of cartilage oligomeric matrix protein, 3B3(-), and
3B3(+) remained above the baseline. Concentrations of these
biomarkers in the knees not operated on did not change
significantly from the baseline. The levels of cartilage
oligomeric matrix protein and 3B3(-) relative to 3B3(+)
remained constant in all knees. In contrast, the level of
5D4 relative to 3B3(+) declined over time in the knee
operated on but remained constant in the knee not operated
on. These results demonstrate a quantitative change in the
molecular components of synovial fluid after meniscectomy,
as well as a qualitative change evinced by an alteration in
the relative proportions of these epitopes. Extensive
analyses showed a strong correlation between serum levels of
3B3(-) from the femoral and cephalic veins; however, serum
3B3(-) was not correlated with synovial fluid 3B3(-). These
findings support the hypothesis that the concentrations of
select cartilage biomarkers in synovial fluid are altered
following meniscectomy and are promising tools for
objectively monitoring the induction of osteoarthritis in
this model system.},
Key = {fds87685}
}
@article{fds87646,
Title = {4. Lindhorst, E, TP Vail, F Guilak, H Wang, LA Setton, V
Vilim, and VB Kraus. 2000. Longitudinal characterization of
synovial fluid biomarkers in the canine meniscectomy model
of osteoarthritis. J Orthop Res 18:269-280.},
Year = {2000},
Key = {fds87646}
}
@article{fds87686,
Author = {AG Clark and JM Jordan and V Vilim and JB Renner and AD Dragomir and G
Luta, VB Kraus},
Title = {Serum cartilage oligomeric matrix protein reflects
osteoarthritis presence and severity: the Johnston County
Osteoarthritis Project.},
Journal = {Arthritis and rheumatism, UNITED STATES},
Volume = {42},
Number = {11},
Pages = {2356-64},
Year = {1999},
Month = {November},
ISSN = {0004-3591},
Keywords = {Aged • Aged, 80 and over • Biological Markers
• Disease Progression • Extracellular Matrix
Proteins • Female • Glycoproteins • Hip Joint
• Humans • Knee Joint • Male • Middle
Aged • Osteoarthritis, Knee • blood • blood*
• radiography},
Abstract = {OBJECTIVE: To characterize serum cartilage oligomeric matrix
protein (COMP) levels by age and gender for a
radiographically defined population free of hip and knee
osteoarthritis (OA), and to examine the potential utility of
COMP as a diagnostic biomarker for knee OA. METHODS: Serum
samples and knee and hip radiographs were obtained at a
baseline evaluation as part of the Johnston County
Osteoarthritis Project, a population-based study of OA in
rural North Carolina. A total of 291 Caucasian participants
were randomly selected for COMP analysis, 143 patients with
radiographic knee OA (Kellgren/Lawrence [K/L] grade > or =
2) and 148 controls with neither hip nor knee OA (K/L grade
0), evenly distributed by age and gender. COMP was
quantified by competitive enzyme-linked immunosorbent assay
with monoclonal antibody 17-C10. The natural log-transformed
COMP data were analyzed using general linear models.
RESULTS: Serum COMP levels were significantly elevated (P =
0.0001) in the age > or = 65 group (mean +/- SD 1,302.1 +/-
496.7 ng/ml) versus the age 45-54 and age 55-64 groups
(1,058.1 +/- 432.4 and 1,038.6 +/- 313.3, respectively).
Serum COMP levels of the OA group were significantly higher
than those of the control group (1,208.57 +/- 487.47 ng/ml
versus 1,061.83 +/- 370.58 ng/ml; P = 0.0093). Serum COMP
levels also increased significantly with knee OA K/L grade
(P = 0.0047), knee OA laterality (P = 0.0043), and number of
knee and hip joints involved (P = 0.0001). There was no
significant difference in serum COMP levels by gender or
obesity. CONCLUSION: We demonstrate that in a
population-based sample, serum COMP levels can distinguish
an OA-affected subgroup from an unaffected subgroup and can
reflect disease severity and multiple joint involvement in
OA.},
Key = {fds87686}
}
@article{fds87666,
Title = {3. Clark, AG, J Jordan, V Vilim, JB Renner, A Dragomir, G
Luta, and VB Kraus. 1999. Serum cartilage oligomeric matrix
protein reflects osteoarthritis presence and severity: the
Johnston County Osteoarthritis Project. Arthritis Rheum
42(11): 2356-2364.},
Year = {1999},
Key = {fds87666}
}
@article{fds87688,
Author = {JL Huebner and IG Otterness and EM Freund and B Caterson and VB
Kraus},
Title = {Collagenase 1 and collagenase 3 expression in a guinea pig
model of osteoarthritis.},
Journal = {Arthritis and rheumatism, UNITED STATES},
Volume = {41},
Number = {5},
Pages = {877-90},
Year = {1998},
Month = {May},
ISSN = {0004-3591},
Keywords = {Animals • Blotting, Southern • Collagenases •
DNA Primers • Disease Models, Animal •
Glyceraldehyde-3-Phosphate Dehydrogenases • Guinea Pigs
• Humans • Immunohistochemistry • Male •
Matrix Metalloproteinase 1 • Matrix Metalloproteinase
13 • Menisci, Tibial • Mice • Osteoarthritis
• Polymerase Chain Reaction • RNA, Messenger
• Rats • Species Specificity • chemistry
• enzymology • enzymology* • etiology •
genetics • metabolism • metabolism* •
pathology},
Abstract = {OBJECTIVE: To analyze the in vivo compartmental expression
of collagenases 1 and 3 (MMP-1 and MMP-13) in the Hartley
guinea pig model of spontaneously occurring osteoarthritis
(OA) for the purpose of elucidating their roles in the
pathogenesis of OA. METHODS: Competitive reverse
transcription-polymerase chain reaction (RT-PCR) and
immunohistochemistry quantification of messenger RNA (mRNA)
and protein levels in medial and lateral tibial cartilage
obtained from the knee joints of 2-month-old (no OA) and
12-month-old (OA) guinea pigs. RESULTS: The patterns of mRNA
expression of collagenases 1 and 3 varied with the age of
the animal and the compartment of the knee. We also found
focal areas of collagenase 1 and collagenase 3 proteins
localized to the extracellular matrix of OA lesion sites,
coincident with three-quarter/one-quarter collagen cleavage.
Collagenase 3 protein was also abundant throughout the
medial tibial cartilage of 2-month-old animals. CONCLUSION:
This represents the first description of bona fide
collagenase 1 in a rodent species. Recent evidence, however,
based on analysis of mitochondrial DNA homologies, suggests
that the guinea pig is not a member of the order Rodentia
and may be more closely allied with lagomorphs. This
taxonomic controversy leaves open to question the issue of
the expression of collagenase 1 in other rodents, such as
mice and rats. The presence of active collagenases 1 and 3
at OA lesion sites is consistent with an important role of
these enzymes in the cartilage degradation of OA in guinea
pigs. The expression of collagenase 3 in medial tibial
cartilage from 2-month-old guinea pigs may signify a role of
this enzyme in cartilage remodeling with growth and
development, or it may represent an early molecular
manifestation of OA.},
Key = {fds87688}
}
@article{fds87665,
Title = {2. Huebner, JL, IG Otterness, EMN Freund, B Caterson and VB
Kraus. 1998. Collagenase-1 and Collagenase-3 Expression in a
Guinea Pig Model of Osteoarthritis. Arthritis Rheum 41(5):
877-890.},
Year = {1998},
Key = {fds87665}
}
@article{fds87659,
Author = {AE Bello and WE Garrett and H Wang and J Lohnes and E DeLong and B
Caterson, VB Kraus},
Title = {Comparison of synovial fluid cartilage marker concentrations
and chondral damage assessed arthroscopically in acute knee
injury.},
Journal = {Osteoarthritis and cartilage / OARS, Osteoarthritis Research
Society, ENGLAND},
Volume = {5},
Number = {6},
Pages = {419-26},
Year = {1997},
Month = {November},
ISSN = {1063-4584},
Keywords = {Acute Disease • Adolescent • Adult •
Arthroscopy • Biological Markers • Cartilage,
Articular • Epitopes • Female •
Glycosaminoglycans • Humans • Injury Severity
Score • Knee Injuries • Male • Middle Aged
• Prospective Studies • Single-Blind Method •
Synovial Fluid • analysis • analysis* •
chemistry* • metabolism* • pathology •
pathology*},
Abstract = {OBJECTIVE: To examine the correlation between synovial fluid
cartilage markers and degree of cartilage damage determined
by arthroscopic evaluation in subjects with acute knee
injury. DESIGN: Chondral damage was quantified using a
validated arthroscopic scoring system in 20 subjects with
effusive acute knee injuries of less then 4 months duration
and no history or radiographic evidence of joint pathology.
Levels of synovial fluid 3B3(-) neoepitope, 3B3(+)
chondroitinase generated epitope of proteoglycan, keratan
sulfate (KS) and hyaluronic acid (HA) were measured by
competitive enzyme-linked immunosorbent assays using
monoclonal antibodies 3B3 and 5D4. Total sulfated
glycosaminoglycan (GAG) was measured by 1,9-dimethylmethylene
blue colorimetric dye-binding assay. RESULTS: We found a
dramatic decrease in levels of 3B3(-) (rs = -0.62, P =
0.004), and GAG (rs = -0.49, P = 0.03) with increasing
chondral damage score; but no correlation of damage score
with 3B3(+), KS or HA levels. CONCLUSION: These data reveal
a change in cartilage metabolism within the first 4 months
of symptomatic knee injury evinced by a significant inverse
correlation of 3B3(-) and GAG levels to chondral lesion
severity. These results suggest that serial measurement of
these synovial fluid markers in the setting of acute knee
injury could predict chondral lesion severity and aid in the
decision to intervene surgically.},
Key = {fds87659}
}
@article{fds87694,
Author = {VB Kraus},
Title = {Pathogenesis and treatment of osteoarthritis.},
Journal = {The Medical clinics of North America, UNITED
STATES},
Volume = {81},
Number = {1},
Pages = {85-112},
Year = {1997},
Month = {January},
ISSN = {0025-7125},
Keywords = {Cartilage, Articular • Disease Progression •
Environment • Feasibility Studies • Humans •
Molecular Biology • Osteoarthritis • Risk Factors
• classification • drug therapy • etiology*
• genetics • pathology},
Abstract = {OA represents the final common pathway of a number of
pathologic processes. The challenge is to define and
classify the subsets of OA to understand the causes and to
devise specific therapies. Effective chondroprotective
therapies will be most useful when applied to high-risk
individuals before the emergence of symptomatic OA. This
will be feasible only with an improved understanding of the
complex interaction of genes and environment in the OA
disease process. Moreover, identifying the heritable bases
of this disease will provide insight into the molecular
mechanisms of the complex pathway that results in OA.
Clinicians who encounter and treat OA patients can look
forward to the development of more effective and innovative
therapies based on a rapidly improving understanding of
OA.},
Key = {fds87694}
}
@article{fds87648,
Title = {Huebner, JL, IG Otterness, EMN Freund, B Caterson and VB
Kraus. 1997. Collagenase-1 and Collagenase-3 Expression in a
Guinea Pig Model of Osteoarthritis. Arthritis Rheum (in
press).},
Year = {1997},
Key = {fds87648}
}
@article{fds87664,
Title = {1. Kraus, VB. 1997. Pathogenesis and Treatment of
Osteoarthritis. Med. Clinics of North Amer. 81(1):
85-112.},
Year = {1997},
Key = {fds87664}
}
@article{fds87671,
Title = {MANUSCRIPTS Bello, AE, WE Garrett, H Wang, J Lohnes, E
DeLong, B Caterson and VB Kraus. 1997. Comparison of
synovial fluid cartilage marker concentrations and chondral
damage assessed arthroscopically in acute knee injury. Osteo
& Cartilage 5(6):419-426.},
Year = {1997},
Key = {fds87671}
}
@article{fds87672,
Title = {ABSTRACTS Lindhorst, E, TP Vail, F Guilak, LA Setton, SP
Scully and VB Kraus. 1997. Longitudinal characterization of
the canine meniscectomy model of osteoarthritis with
cartilage biomarkers. Trans Ortho Res Soc 22: 425. Huebner,
JL, EMN Freund, B Caterson, and VB Kraus. 1997.
Identification and localization of collagenase in a guinea
pig model of osteoarthritis. Trans Ortho Res Soc 22: 172.
Kraus, VB, N Gell and H Wang. 1997. Pilot study of bone and
cartilage serum biomarkers with aquatic exercise. (poster
and podium presentation) Arthritis Research Conference
co-sponsored by ACR, AF and NIAMS, C18. Kraus, VB and AE
Clark. 1997. Selective uptake of aggrecan fragments by
arthritic synovial fibroblasts. 1997. Arthritis Research
Conference co-sponsored by ACR, AF and NIAMS, P56. Huebner,
JL and VB Kraus. 1998. Collagenase-3 expression in a guinea
pig model of osteoarthritis. 44th Annual Meeting of the
Orthopaedic Research Society, New Orleans. (accepted) Clark,
AG, V Vilim and VB Kraus. 1998. Production of cartilage
oligomeric matrix protein MRNA and protein by cultured human
synovial fibroblasts. 44th Annual Meeting of the Orthopaedic
Research Society, New Orleans. (accepted) Lindhorst, E, F
Guilak, SP Scully, TP Vail, V Vilim, A Smitten and VB Kraus.
1998. Allograft reconstruction of the medial meniscus
prevents synovial fluid biomarker elevations following total
meniscectomy. 44th Annual Meeting of the Orthopaedic
Research Society, New Orleans. (accepted, podium
presentation).},
Year = {1997},
Key = {fds87672}
}
@article{fds87670,
Title = {Kraus, V.M.B., C.E. Hughes, P. Neame, D. Heinegard, J.
Dudhia, T. Hardingham, and B. Caterson. 1996. Production and
characterization of a novel monoclonal antibody to the G3
domain of cartilage aggrecan. Trans. Orthop. Res. Soc. 22:
763.},
Year = {1996},
Key = {fds87670}
}
@article{fds87663,
Author = {VB Kraus and JA Inostroza and K Yeung and D Reinberg, JR
Nevins},
Title = {Interaction of the Dr1 inhibitory factor with the TATA
binding protein is disrupted by adenovirus
E1A.},
Journal = {Proceedings of the National Academy of Sciences of the
United States of America, UNITED STATES},
Volume = {91},
Number = {14},
Pages = {6279-82},
Year = {1994},
Month = {July},
ISSN = {0027-8424},
Keywords = {Adenovirus E1A Proteins • Animals • DNA-Binding
Proteins • Glutathione Transferase • Heat-Shock
Proteins • Hela Cells • Humans • Luciferases
• Phosphoproteins • Rabbits • Recombinant
Fusion Proteins • TATA Box • TATA-Box Binding
Protein • Transcription Factors • Transcription,
Genetic • Transfection • biosynthesis •
isolation & purification • metabolism •
metabolism*},
Abstract = {Past experiments have shown that the adenovirus E1A12S
product activates the hsp70 promoter, dependent on the TATA
element and dependent on N-terminal E1A sequences. Other
experiments have identified a factor termed Dr1 that
interacts with and inhibits the transcriptional activity of
the TATA-binding protein (TBP). We now find that the E1A12S
protein can disrupt the interaction of the Dr1 factor with
the TATA-specific TBP factor, allowing the productive
interaction of TBP with TFIIA. This E1A-mediated disruption
is dependent on N-terminal sequences that are also essential
for the TATA-dependent trans-activation of the hsp70
promoter. Moreover, we also find that Dr1 expression in
transfected cells can inhibit transcription from the hsp70
promoter and that this can be overcome by coexpression of
the wild-type E1A protein, dependent on N-terminal
sequences. We conclude that the activation of hsp70 through
the TATA element may be mechanistically similar to the
activation of the E2 promoter via E2F, in each case
involving a release of a transcription factor from an
inactive complex.},
Key = {fds87663}
}
@article{fds87647,
Title = {Kraus, V.B., C.H. Hughes and B. Caterson. 1994. Uptake of
chondroitin-sulfate bearing fragments of cartilage aggrecan
by rheumatoid and osteoarthritic synovial fibroblasts.
Arthritis & Rheumatism 37(9) Suppl.: S192.},
Year = {1994},
Key = {fds87647}
}
@article{fds87669,
Title = {Kraus, V.B., J.A. Inostroza, K. Yeung, D. Reinberg, and J.R.
Nevins. 1994. Interaction of the Dr1 inhibitory factor with
the TATA binding protein is disrupted by adenovirus E1A.
Proc. Nat'l. Acad. Sci. USA. 91:6279-6282.},
Year = {1994},
Key = {fds87669}
}
@article{fds87696,
Author = {DA Taylor and VB Kraus and JJ Schwarz and EN Olson and WE
Kraus},
Title = {E1A-mediated inhibition of myogenesis correlates with a
direct physical interaction of E1A12S and basic
helix-loop-helix proteins.},
Journal = {Molecular and cellular biology, UNITED STATES},
Volume = {13},
Number = {8},
Pages = {4714-27},
Year = {1993},
Month = {August},
ISSN = {0270-7306},
Keywords = {Adenovirus E1A Proteins • Base Sequence • Cell
Differentiation • Creatine Kinase • DNA-Binding
Proteins • Enhancer Elements (Genetics) • Gene
Expression Regulation • Humans • Molecular
Sequence Data • Muscle Proteins • Muscles •
Myogenin • Oligodeoxyribonucleotides • Protein
Binding • Recombinant Fusion Proteins • Repressor
Proteins • Structure-Activity Relationship •
Transcription Factors • Transcription, Genetic •
Tumor Cells, Cultured • chemistry • cytology*
• genetics* • metabolism*},
Abstract = {The observation that adenovirus E1A gene products can
inhibit differentiation of skeletal myocytes suggested that
E1A may interfere with the activity of myogenic basic
helix-loop-helix (bHLH) transcription factors. We have
examined the ability of E1A to mediate repression of the
muscle-specific creatine kinase (MCK) gene. Both the E1A12S
and E1A13S products repressed MCK transcription in a
concentration-dependent fashion. In contrast, amino-terminal
deletion mutants (d2-36 and d15-35) of E1A12S were defective
for repression. E1A12S also repressed expression of a
promoter containing a multimer of the MCK high-affinity E
box (the consensus site for myogenic bHLH protein binding)
that was dependent, in C3H10T1/2 cells, on coexpression of a
myogenin bHLH-VP16 fusion protein. A series of
coprecipitation experiments with glutathione S-transferase
fusion and in vitro-translated proteins demonstrated that
E1A12S, but not amino-terminal E1A deletion mutants, could
bind to full-length myogenin and E12 and to deletion mutants
of myogenin and E12 that spare the bHLH domains. Thus, the
bHLH domains of myogenin and E12, and the high-affinity E
box, are targets for E1A-mediated repression of the MCK
enhancer, and domains of E1A required for repression of
muscle-specific gene transcription also mediate binding to
bHLH proteins. We conclude that E1A mediates repression of
muscle-specific gene transcription through its
amino-terminal domain and propose that this may involve a
direct physical interaction between E1A and the bHLH region
of myogenic determination proteins.},
Key = {fds87696}
}
@article{fds87667,
Title = {Taylor, D.A., V.B. Kraus, J.J. Schwarz, E.N. Olson, and W.E.
Kraus. 1993. E1A-mediated inhibition of myogenesis
correlates with a direct physical interaction of E1A12S and
basic-helix-loop-helix proteins. Mol. Cell. Biol.
13:4714-4727.},
Year = {1993},
Key = {fds87667}
}
@article{fds87668,
Title = {Kraus, V.M.B. 1993. Transcriptional control mechanisms by
E1A and E1A-like DNA tumor viral oncoproteins. Ph.D. Thesis.
Duke University.},
Year = {1993},
Key = {fds87668}
}
@article{fds87691,
Author = {VB Kraus and E Moran, JR Nevins},
Title = {Promoter-specific trans-activation by the adenovirus E1A12S
product involves separate E1A domains.},
Journal = {Molecular and cellular biology, UNITED STATES},
Volume = {12},
Number = {10},
Pages = {4391-9},
Year = {1992},
Month = {October},
ISSN = {0270-7306},
Keywords = {Adenovirus E1A Proteins • Binding Sites •
Blotting, Western • Cell Line • Cloning, Molecular
• Heat-Shock Proteins • Precipitin Tests •
Promoter Regions (Genetics)* • Trans-Activation
(Genetics)* • Trans-Activators • Transfection
• chemistry • genetics • genetics* •
metabolism*},
Abstract = {Recent studies have shown that the adenovirus E1A12S product
can trans-activate transcription by activating the
transcription factor E2F. However, E2F cannot be the only
target for the E1A12S product, since several cellular
promoters have been found to be activated by the E1A12S
protein even though they lack E2F sites. Indeed, we now show
that activation of the hsp70 promoter by the E1A12S product
requires the TATAA sequence. Moreover, activation of the
hsp70 promoter requires the N-terminal domain of the E1A
protein and does not require the conserved region 2
sequences which are required for the E2F-dependent
activation of transcription. We conclude that the targeting
of distinct transcription factors, leading to
trans-activation of transcription of multiple promoters,
involves distinct domains of the E1A proteins that are also
required for oncogenic activity.},
Key = {fds87691}
}
@article{fds87657,
Author = {S Chellappan and VB Kraus and B Kroger and K Munger and PM Howley and WC
Phelps, JR Nevins},
Title = {Adenovirus E1A, simian virus 40 tumor antigen, and human
papillomavirus E7 protein share the capacity to disrupt the
interaction between transcription factor E2F and the
retinoblastoma gene product.},
Journal = {Proceedings of the National Academy of Sciences of the
United States of America, UNITED STATES},
Volume = {89},
Number = {10},
Pages = {4549-53},
Year = {1992},
Month = {May},
ISSN = {0027-8424},
Keywords = {Adenovirus Early Proteins • Amino Acid Sequence •
Antigens, Polyomavirus Transforming • Carrier Proteins*
• Cell Cycle Proteins* • Cell Line • Cell
Line, Transformed • Cyclins • DNA-Binding
Proteins* • E2F Transcription Factors • Female
• Genes, Retinoblastoma • Glutathione Transferase
• Hela Cells • Humans • Molecular Sequence
Data • Oncogene Proteins, Viral • Papillomaviridae
• Recombinant Fusion Proteins • Retinoblastoma
Protein • Sequence Homology, Nucleic Acid • Simian
virus 40 • Transcription Factor DP1 •
Transcription Factors • Uterine Cervical Neoplasms
• genetics • isolation & purification •
metabolism • metabolism*},
Abstract = {The adenovirus E1A gene product, the simian virus 40 large
tumor antigen, and the human papillomavirus E7 protein share
a short amino acid sequence that constitutes a domain
required for the transforming activity of these proteins.
These sequences are also required for these proteins to bind
to the retinoblastoma gene product (pRb). Recent experiments
have shown that E1A can dissociate complexes containing the
transcription factor E2F bound to pRb, dependent on this
conserved sequence element. We now show that the E7 protein
and the simian virus 40 large tumor antigen can dissociate
the E2F-pRb complex, dependent on this conserved sequence
element. We also find that the E2F-pRb complex is absent in
various human cervical carcinoma cell lines that either
express the E7 protein or harbor an RB1 mutation, suggesting
that the loss of the E2F-pRb interaction may be an important
aspect in human cervical carcinogenesis. We suggest that the
ability of E1A, the simian virus 40 large tumor antigen, and
E7 to dissociate the E2F-pRb complex may be a common
activity of these viral proteins that has evolved to
stimulate quiescent cells into a proliferating state so that
viral replication can proceed efficiently. In circumstances
in which a lytic infection does not proceed, the consequence
of this action may be to initiate the oncogenic process in a
manner analogous to the mutation of the RB1
gene.},
Key = {fds87657}
}
@article{fds87706,
Author = {P Raychaudhuri and S Bagchi and SH Devoto and VB Kraus and E Moran, JR
Nevins},
Title = {Domains of the adenovirus E1A protein required for oncogenic
activity are also required for dissociation of E2F
transcription factor complexes.},
Journal = {Genes & development, UNITED STATES},
Volume = {5},
Number = {7},
Pages = {1200-11},
Year = {1991},
Month = {July},
ISSN = {0890-9369},
Keywords = {Adenoviridae • Adenovirus Early Proteins • Amino
Acid Sequence • Animals • Base Sequence •
Binding, Competitive • Carrier Proteins* • Cell
Cycle Proteins* • Cyclins • DNA-Binding Proteins*
• E2F Transcription Factors • L Cells (Cell Line)
• Mice • Oncogene Proteins, Viral • Teratoma
• Trans-Activation (Genetics) • Transcription
Factor DP1 • Transcription Factors • antagonists &
inhibitors • genetics • genetics* •
physiology • physiology*},
Abstract = {Recent experiments have shown that the cellular E2F
transcription factor is found in complexes with cellular
proteins and that one such complex contains the cyclin-A
protein. Isolation of a cellular activity, which we term
E2F-BF, can reconstitute the E2F-cyclin-A complex and has
permitted a more detailed analysis of the mechanism of E1A
dissociation. Through the analysis of a series of E1A
mutants, we find that sequences in conserved region 1 (CR1)
and conserved region 2 (CR2) are important for dissociation
of the E2F complex, whereas amino-terminal sequences are not
required. In contrast to the requirements for dissociation,
only the CR1 sequences are required to block formation of
the complex if E1A is added when the components are
combined. We have also identified an activity, termed E2F-I,
that inhibits E2F binding to DNA, again apparently through
the formation of a complex with E2F. This inhibitory
activity is also blocked by E1A, dependent on the same
elements of the E1A protein that disrupt the interaction
with E2F-BF. Because the E1A sequences that are important
for releasing E2F from these interactions are also sequences
necessary for oncogenesis, we suggest that this activity may
be a critical component of the transforming activity of
E1A.},
Key = {fds87706}
}
@article{fds87656,
Author = {S Manzi and VB Kraus and EW St Clair},
Title = {An unusual photoactivated skin eruption. Quinidine-induced
livedo reticularis.},
Journal = {Archives of dermatology, UNITED STATES},
Volume = {125},
Number = {3},
Pages = {417-8, 421-2},
Year = {1989},
Month = {March},
ISSN = {0003-987X},
Keywords = {Epidermis • Female • Humans • Middle Aged
• Necrosis • Photosensitivity Disorders •
Quinidine • Skin • adverse effects* • blood
supply* • chemically induced* •
pathology},
Key = {fds87656}
}
@article{fds87689,
Author = {VB Kraus and EA Harden and B Wittels and JO Moore and BF
Haynes},
Title = {Demonstration of phenotypic abnormalities of thymic
epithelium in thymoma including two cases with abundant
Langerhans cells.},
Journal = {The American journal of pathology, UNITED
STATES},
Volume = {132},
Number = {3},
Pages = {552-62},
Year = {1988},
Month = {September},
ISSN = {0002-9440},
Keywords = {Adult • Aged • Antibodies, Monoclonal •
Antigens, Differentiation, T-Lymphocyte • Epithelium
• Female • Humans • Langerhans Cells •
Male • Middle Aged • Myasthenia Gravis •
Phenotype • Thymoma • Thymus Neoplasms •
immunology • pathology • pathology*},
Abstract = {A panel of monoclonal antibodies that phenotypically define
stages of normal human thymic epithelial (TE) cell
maturation was used to compare thymic epithelium of nine
thymomas with hyperplastic thymic epithelium in myasthenia
gravis (MG) and thymic epithelium of normal thymuses. It has
been shown previously that normal thymic epithelial cells
express antigens of early TE cell maturation (A2B5, TE-4)
throughout thymic ontogeny and acquire antigens 12/1-2, TE8,
and TE-15 at 14 to 16 weeks of fetal gestation. Hyperplastic
MG thymic epithelial cells expressed TE antigens in
phenotypic patterns similar to that seen in normal postnatal
thymus, ie, TE in subcapsular cortex and medulla was TE4+,
A2B5+, and 12/1 - 2+ and Hassall's bodies were reactive with
antibodies TE8 and TE15. In contrast, thymic epithelium in
primary mediastinal thymomas was TE4+, A2B5+, TE8-, and
greater than 75% of thymoma epithelium was 12/1 - 2-, a
thymic epithelial phenotype similar to that seen on normal
fetal thymic epithelium at 14 to 16 weeks fetal gestation.
In one subject with a mature epithelial histologic pattern,
thymoma epithelium was found to be strongly TE8+, a
phenotype suggestive of a later stage of TE maturation.
Lymphocytes in five of seven thymomas with immature thymic
epithelial cells predominantly expressed immature thymocyte
phenotype while two thymomas with immature epithelial
phenotype showed a predominance of Langerhans cells and
surrounding lymphocytes expressing a mature phenotype.
Lymphocytes in the thymoma with differentiated epithelial
cells expressed a mature thymocyte phenotype. Thus, in
thymomas of varying histologic types, phenotypic
abnormalities of thymic epithelium are present; these
phenotypic abnormalities may reflect abnormal thymic
epithelial maturation.},
Key = {fds87689}
}
@article{fds87701,
Author = {VB Kraus and JN Baraniuk and GB Hill and NB Allen},
Title = {Ureaplasma urealyticum septic arthritis in
hypogammaglobulinemia.},
Journal = {The Journal of rheumatology, CANADA},
Volume = {15},
Number = {2},
Pages = {369-71},
Year = {1988},
Month = {February},
ISSN = {0315-162X},
Keywords = {Adult • Agammaglobulinemia • Arthritis, Infectious
• Bacterial Infections • Doxycycline • Humans
• Male • Pelvis • Streptomycin •
Tetracycline Resistance • Ureaplasma •
complications* • drug therapy • microbiology
• radiography • therapeutic use},
Abstract = {We describe a hypogammaglobulinemic man with erosive
oligoarticular septic arthritis due to Ureaplasma
urealyticum. His clinical course was complicated by a
subcutaneous abscess. Multiple synovial cultures were
negative until finally cultures specific for mycoplasmas
were performed. Serologic diagnosis cannot be relied upon in
hypogammaglobulinemic patients because they do not mount a
perceptible antibody response. This underscores the
importance of a high clinical suspicion of mycoplasmas as
etiologic agents of septic arthritis in this population and
early communication with the microbiology laboratory so that
appropriate cultures for mycoplasmas can be performed and
joint destruction minimized.},
Key = {fds87701}
}
@article{fds87710,
Author = {VB Kraus and WJ Fulkerson and MA Gowen and WM Samuelson},
Title = {Straw lung.},
Journal = {The New England journal of medicine, UNITED
STATES},
Volume = {312},
Number = {14},
Pages = {924},
Year = {1985},
Month = {April},
ISSN = {0028-4793},
Keywords = {Adult • Female • Foreign Bodies • Humans
• Lung* • Plastics* • diagnosis*},
Key = {fds87710}
}
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