Xu Lin, Servais Jacqueline, Polur Ilona, Kim Doil, Lee Peter L, Chung Kimberly, Li Yefu
Harvard School of Dental Medicine, Boston, Massachusetts 02115, USA.
Arthritis Rheum. 2010 Sep;62(9):2736-44. doi: 10.1002/art.27582.
To investigate whether the reduction of discoidin domain receptor 2 (DDR-2), a cell membrane tyrosine kinase receptor for native type II collagen, attenuates the progression of articular cartilage degeneration in mouse models of osteoarthritis (OA).
Double-heterozygous (type XI collagen-deficient [Col11a1(+/-)] and Ddr2-deficient [Ddr2(+/-)]) mutant mice were generated. Knee joints of Ddr2(+/-) mice were subjected to microsurgical destabilization of the medial meniscus. Conditions of the articular cartilage from the knee joints of the double-heterozygous mutant and surgically treated mice were examined by histology, evaluated using a modified Mankin scoring system, and characterized by immunohistochemistry.
The rate of progressive degeneration in knee joints was dramatically reduced in the double-heterozygous mutant mice compared with that in the type XI collagen-deficient mice. The progression in the double-heterozygous mutant mice was delayed by ∼6 months. Following surgical destabilization of the medial meniscus, the progressive degeneration toward OA was dramatically delayed in the Ddr2(+/-) mice compared with that in their wild-type littermates. The articular cartilage damage present in the knee joints of the mice was directly correlated with the expression profiles of DDR-2 and matrix metalloproteinase 13.
Reduction of DDR-2 expression attenuates the articular cartilage degeneration of knee joints induced either by type XI collagen deficiency or by surgical destabilization of the medial meniscus.
研究盘状结构域受体2（DDR-2，一种天然II型胶原蛋白的细胞膜酪氨酸激酶受体）的减少是否会减缓骨关节炎（OA）小鼠模型中关节软骨退变的进程。
培育双杂合子（XI型胶原蛋白缺陷[Col11a1(+/-)]和Ddr2缺陷[Ddr2(+/-)]）突变小鼠。对Ddr2(+/-)小鼠的膝关节进行内侧半月板显微手术失稳处理。通过组织学检查双杂合子突变小鼠和手术处理小鼠膝关节的关节软骨状况，使用改良的曼金评分系统进行评估，并通过免疫组织化学进行表征。
与XI型胶原蛋白缺陷小鼠相比，双杂合子突变小鼠膝关节的渐进性退变速率显著降低。双杂合子突变小鼠的退变进程延迟了约6个月。在内侧半月板手术失稳后，与野生型同窝小鼠相比，Ddr2(+/-)小鼠向OA的渐进性退变显著延迟。小鼠膝关节中存在的关节软骨损伤与DDR-2和基质金属蛋白酶13的表达谱直接相关。
DDR-2表达的降低可减缓由XI型胶原蛋白缺乏或内侧半月板手术失稳诱导的膝关节关节软骨退变。
