关节软骨细胞衰老在关节软骨退变和骨关节炎(Osteoarthritis,OA)病程中起重要作用，但引起软骨细胞衰老的机制尚未阐明。本课题组前期研究发现老年小鼠(24月龄)膝关节软骨细胞中FBXW7(泛素化连接酶)表达较年轻小鼠(3月龄)明显下调，沉默FBXW7能促进原代软骨细胞衰老相关指标表达增高，软骨细胞敲除FBXW7可加速小鼠OA进展，提示FBXW7可能抑制软骨细胞衰老和OA的发生发展。本项目拟通过沉默或过表达FBXW7，进一步确定其在软骨细胞中的生物学功能及其对软骨细胞衰老的影响。利用软骨细胞敲除FBXW7基因的小鼠模型和OA临床样本，明确FBXW7对关节软骨退变及OA病程的影响，联合iTRAQ分析及信号通路芯片检测结果，探索FBXW7调控软骨细胞衰老参与OA的可能机制。本项目有望为软骨细胞衰老与OA的发生机制提供新观点，为延缓软骨细胞衰老提供新思路和防治OA提供新的潜在靶标。

Chondrocyte senescence plays a crucial role in articular cartilage degeneration and osteoarthritis (OA) progression, but the mechanism has not been clarified. We discovered the lost expression of FBXW7 in articular cartilage of aged mice (24 months), which was abundantly expressed in younger mice (3 months). The absence of FBXW7 could promote primary chondrocyte towards to senescence. Moreover, knocking out FBXW7 in chondrocytes accelerated the progression of OA, implicating that FBXW7 could probably inhibit the senescence of chondrocytes and the progression of OA. This project aims to confirm the biological function of FBXW7 in chondrocyte senescence via depressing or over expressing FBXW7. Combined the use of transgenic mice model with clinical OA samples, we are going to demonstrate the role of FBXW7 in chondrocyte senescence and OA progression. Through iTRAQ analysis and signal pathway chip detection, we are going to explore the cellular and molecular mechanisms of FBXW7 in the chondrocyte senescence and the pathogenesis of OA, providing a new perspective for suspending chondrocyte senescence and a new potential target for the treatment of OA.