Hu K, Xu L, Cao L, Flahiff C M, Brussiau J, Ho K, Setton L A, Youn I, Guilak F, Olsen B R, Li Y
Harvard School of Dental Medicine, Boston, Massachusetts 02115, USA.
Arthritis Rheum. 2006 Sep;54(9):2891-900. doi: 10.1002/art.22040.
To examine the pathogenetic mechanisms of osteoarthritis (OA)-like changes in Col9a1-/- mice, which are deficient in type IX collagen.
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.
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.
Lack of type IX collagen in Col9a1-/- mice results in age-dependent OA-like changes in the knee joints and TMJs.
研究缺乏IX型胶原蛋白的Col9a1-/-小鼠骨关节炎（OA）样改变的发病机制。
对Col9a1-/-小鼠及其野生型（Col9a1+/+）同窝小鼠的膝关节和颞下颌关节（TMJ）进行光学显微镜检查。采用免疫组织化学染色法检测膝关节中基质金属蛋白酶3（MMP-3）、MMP-13、降解的II型胶原蛋白和盘状结构域受体2（DDR-2）的表达。还通过胫骨平台的微压痕试验评估软骨力学的压缩性能，通过股骨髁的渗透压加载评估拉伸性能。
组织学分析显示，Col9a1-/-小鼠在3个月大时膝关节和TMJ出现年龄依赖性OA样改变。6个月大时，在突变小鼠的膝关节和TMJ的关节软骨中观察到蛋白聚糖降解增强。6个月大时，Col9a1-/-小鼠膝关节中MMP-13和DDR-2蛋白的表达以及降解的II型胶原蛋白的量均高于其野生型同窝小鼠。6个月大时，在Col9a1-/-小鼠的股骨和胫骨平台观察到软骨力学变化，包括压缩模量和单轴模量降低。在3个月和6个月大时，发现Col9a1-/-小鼠的胫骨软骨对流体流动的渗透性更高，且与负载支撑的流体加压机制相关受损。所有这些变化仅发生在内侧部位。
Col9a1-/-小鼠缺乏IX型胶原蛋白会导致膝关节和TMJ出现年龄依赖性OA样改变。
