Activation of β-catenin in Col2-expressing chondrocytes leads to osteoarthritis-like defects in hip joint
Activation of β-catenin in Col2-expressing chondrocytes leads to osteoarthritis-like defects in hip joint
复制标题
表达 Col2 的软骨细胞中 β-连环蛋白的激活导致髋关节骨关节炎样缺陷
DOI：
10.1002/jcp.28491
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发表时间：
2019-10-01
影响因子：
5.6
通讯作者：
Jin, Hongting
中科院分区：
文献类型：
--
作者：
Xia, Chenjie;Wang, Pinger;Jin, Hongting
尽管髋关节骨关节炎（OA）是一种常见的使人衰弱的退行性疾病，但其病理过程的确切分子机制尚不清楚。本研究旨在探讨β -连环蛋白是否在髋关节骨关节炎发病中起关键作用。在这里，我们发现-连环蛋白在人OA软骨组织中过表达。然后，我们分析了β -catenin基因在股骨头软骨细胞中有条件激活的β -cat(ex3)（Col2ER）小鼠。在2个月大时，β -cat(ex3)（Col2ER）小鼠已经显示出股骨头严重软骨变性的表型。随着年龄的增长，在β -cat(ex3)（Col2ER）小鼠中观察到的更多变化包括软骨下硬化症和沿关节边缘形成的骨赘，类似于人类髋关节OA表型。此外，作为β -连环蛋白激活的结果，软骨降解和软骨细胞凋亡可能促成了这种髋关节oa样表型。总的来说，我们的发现为β -连环蛋白在髋OA发病机制中的重要性提供了直接证据。
Although osteoarthritis (OA) in the hip joint is a common and debilitating degenerative disease, the precise molecular mechanisms underlying its pathological process remains unclear. This study sets out to investigate whether beta-catenin plays a critical role in hip OA pathogenesis. Here, we showed overexpressed beta-catenin protein in human OA cartilage tissues. Then, we analyzed beta-cat(ex3)(Col2ER) mice, in which beta-catenin gene was conditionally activated in femoral head chondrocytes. At 2 months of age, beta-cat(ex3)(Col2ER) mice already showed a phenotype of severe cartilage degeneration in the femoral head. More changes observed in beta-cat(ex3)(Col2ER) mice with age included subchondral sclerosis and osteophyte formation along joint margins, resembling a hip OA phenotype in humans. In addition, cartilage degradation and chondrocyte apoptosis as the results of beta-catenin activation possibly contributed to this hip OA-like phenotype. Overall our findings provide direct evidence about the importance of beta-catenin in hip OA pathogenesis.