DHEA调控原位纤毛Hh信号通路抑制软骨细胞衰老在骨关节炎中的作用及机制研究

骨关节炎是中老年人中常见的衰老相关退行性疾病，软骨细胞衰老在骨关节炎发病机制中作用突出，研究软骨细胞衰老调控机制是目前疾病早期治疗的希望。脱氢表雄酮（DHEA）是著名的“抗衰老”类固醇激素。我们前期发现DHEA能通过抑制软骨细胞衰老对OA起保护作用。在此基础上，发现DHEA对软骨细胞衰老调控可能是通过原位纤毛Hh信号通路，且与通路上的膜受体蛋白SMO活性相关。但该表型需进一步更全面的论证，并且DHEA影响SMO活性调控原位纤毛Hh信号通路在软骨细胞衰老的具体机制需要深入研究。本项目基于原有基础，拟：（1）验证DHEA调控软骨细胞衰老对OA的影响（2）验证DHEA调控原位纤毛Hh信号通路影响软骨细胞衰老（3）探索DHEA通过SMO调控原位纤毛Hh信号通路影响软骨细胞衰老的机制。本研究可以对骨关节炎中软骨细胞衰老的调控机制带来新的认识，可能为骨关节炎早期治疗带来新的策略。

Osteoarthritis (OA) is a common aging related degenerative disease in middle-aged and elderly people. Chondrocyte senescence plays an important role in the pathogenesis of osteoarthritis. To study the role of chondrocyte senescence in the pathogenesis of OA is the hope to change the disease in the early stage. Dehydroepiandrosterone (DHEA) is a well-known "anti-aging" steroid hormone. We found that DHEA could protect OA by inhibiting chondrocyte senescence. DHEA may regulate chondrocyte senescence through ciliary Hh signaling pathway, and its mechanism is related to the activity of membrane receptor protein SMO. However, this phenotype needs further and more comprehensive demonstration, and the specific mechanism of DHEA affecting SMO activity and regulating ciliary Hh signaling pathway in chondrocyte senescence needs further study. Based on our previous basis, this project is to: (1) clarify the effect of DHEA on OA by regulating chondrocyte senescence; (2) clarify the effect of DHEA on chondrocyte senescence by regulating ciliary Hh signaling pathway; (3) explore the mechanism of DHEA on chondrocyte senescence by regulating ciliary Hh signaling pathway via SMO. This study can bring a new understanding of the regulatory mechanism of chondrocyte senescence in OA, and may bring new strategies for the early treatment of OA.