骨性关节炎(Osteoarthritis，OA)是一种发生机制不清，尚无有效防治手段的高发疾病。前期研究发现Annexin 5（A5）是一种可控细胞内、外钙离子浓度的胞浆蛋白，正常软骨细胞中无A5存在，而在OA患者软骨细胞中A5则大量聚集，但两者是否有相互作用尚无研究涉入；本课题组预实验提示过度表达A5的正常软骨细胞其终末分化相关基因表达明显上调，且胞内Wnt信号被过度抑制，而NF-kB通路明显激活；结合A5最新研究进展，提出A5对双钙离子通道的调控，导致Wnt通路抑制和NF-kB通路激活，进而导致了软骨细胞的终末分化，最终形成OA，且OA特殊内环境状态又维持了A5过度表达的假说；本项目拟用正常及A5基因敲除小鼠进行体内OA模型诱导及体外细胞与组织培养的方法，探索并证实A5在OA发生、发展过程中的重要作用，对阐明A5作用以及揭示OA机制有重要意义，为OA的防治提供一种新思路和理论基础。

Osteoarthritis (OA) is the most common type of degenerative joint diseases. It is a common chronic, progressive musculoskeletal disorder characterized by gradual loss of articular cartilage. OA is regarded as a complex disease whose cause is not completely understood yet, and so far there is no cure for OA. Recent studies revealed that Annexin 5 was highly expressed in the OA chondrocytes, while not in the healthy ones. And then the terminal differentiated markers, such as Apase, MMP13 and Runx-2 of the normal chondrocytes were also upregulated by the Annexin 5 vector transfected chondrocytes from our preliminary data. All those data was indicating the chondrocytes in the status of terminal differentiation, which loss the biological function of the chondrocyte. However, until now there was no research focus on the involved signaling mechanism of Annexin 5. Our preliminary data demonstrated the Wnt luciferase activity was inhibited, and simultaneously NF-kB signaling was activated in the overexpressed Annexin 5 groups. Depletion of Annexin 5 could be a considered and possible method to preserve the chondrocytes biological function out of the terminal differentiation, or the challenge from the OA. This program to investigate the mechanism of Annexin 5 leading articular chondrocytes to terminal differentiation. In this study, use the Annexin 5 gene knock-out mouse model, and observe the signaling pathway changes in vitro and vivo. Effecting on the Wnt and NF-kB pathways of the Annexin 5 may reveal its great role in the OA progress. Inhibiting Annexin 5 could be the next therapeutic target for OA treatments in future.