骨关节炎（Osteoarthritis，OA）是最常见的关节疾病，关节软骨破坏是其最明显的病理特征，然而关节软骨破坏及骨关节炎的发病机理尚未阐明，临床上缺乏有效的防治方法。Src蛋白激酶家族（Src family tyrosine kinase, SFKs）是调控软骨细胞增殖分化的关键信号分子，但其活性改变在骨关节炎发生发展中的作用有待研究。我们的前期研究发现，作为SFKs家族重要成员之一的Fyn在骨关节炎关节软骨中表达水平明显上调，抑制其活性能显著缓解骨关节炎进程，提示关节软骨细胞中Fyn活性改变可能在骨关节炎发生与发展中起重要作用。本课题拟通过临床标本、Fyn全身敲除小鼠模型以及可诱导型软骨细胞特异性敲除小鼠模型，深入探讨软骨细胞Fyn活性改变在骨关节炎病程中的作用及其分子机制，为防治骨关节炎提供新的潜在靶点。

Osteoarthritis (OA) is the most common joint disease characterized by a loss of articular cartilage. However, the underlying mechanisms of cartilage loss and OA development have not yet been fully elucidated. There is also lack of effective therapy methods in clinic. Src family tyrosine kinase (SFKs) serves as a central regulator of cell growth and proliferation, but its role in OA development needs further investigation. Our preliminary results demonstrate that Fyn, As one major member of SFKs, is highly upregulated and activated in OA articular chondrocytes, inhibition of Fyn alleviated cartilage degeneration and loss in OA, implicating an important of Fyn in the pathogenesis of OA. Using Fyn knockout mice and OA mice as models, combined with samples of OA patients and normal population, this project aims to investigate the role and regulation mechanism of chondrocyte Fyn in the pathogenesis of OA on the molecular, cellular and animal levels. The study will provide potential target for prevention and treatment of OA.