- K. Hu and L. Xu and L. Cao and C. M. Flahiff and J. Brussiau and K. Ho and L. A. Setton and I. Youn and F. Guilak and B. R. Olsen and Y. Li, Pathogenesis of osteoarthritis-like changes in the joints of mice deficient in type IX collagen,
Arthritis And Rheumatism, vol. 54 no. 9
pp. 2891 -- 2900 .
(last updated on 2009/09/02)
Objective. To examine the pathogenetic mechanisms of osteoarthritis (OA)-like changes in Col9a1(-/-) mice, which are deficient in type IX collagen. Methods. Knee joints and temporomandibular joints (TMJs) from Col9a1(-/-) mice and their wild-type (Col9a1(+/+)) littermates were examined by light microscopy. Immunohistochemical staining was performed to examine the expression of matrix metalloproteinase 3 (MMP-3) and MMP-13, degraded type II collagen, and the discoidin domain receptor 2 (DDR-2) in knee joints. Cartilage mechanics were also evaluated for compressive properties by microindentation testing of the tibial plateau and for tensile properties by osmotic loading of the femoral condyle. Results. Histologic analysis showed age-dependent OA-like changes in the knee and TMJs of Col9a1(-/-) mice starting at the age of 3 months. At the age of 6 months, enhanced proteoglycan degradation was observed in the articular cartilage of the knee and TMJs of the mutant mice. The expression of MMP-13 and DDR-2 protein and the amount of degraded type II collagen were higher in the knee joints of Col9a1(-/-) mice than in their wild-type littermates at the age of 6 months. Changes in cartilage mechanics were observed in the femoral and tibial plateaus of Col9a1(-/-) mice at 6 months, including a decrease in the compressive modulus and uniaxial modulus. At 3 and 6 months of age, tibial cartilage in Col9a1(-/-) mice was found to be more permeable to fluid flow, with an associated compromise in the fluid pressurization mechanism of load support. All of these changes occurred only at medial sites. Conclusion. Lack of type IX collagen in Col9a1(-/-) mice results in age-dependent OA-like changes in the knee joints and TMJs.