骨性关节炎（osteoarthritis， OA）是一种关节退行性疾病。研究表明补体替代途径在OA发病过程中起到了中心作用。通过调节补体系统活性成为治疗OA的新途径。前期研究表明硫酸软骨素（chondroitin sulfate，CS）具有良好的调节补体和防治OA的作用，但是CS结构、来源、相对分子质量等性质使其活性呈现出多样性，其作用机制也不清楚。本研究拟通过对不同结构、不同片段的CS筛选，找到CS的最佳结构以及作用片段。利用体外、体内实验揭示CS通过调节补体系统治疗OA的机制，最终为OA的治疗提供一种新的策略。.本课题主要内容包括：①制备不同的CS寡糖并进行理化性质表征；②具有特异性抗补体活性CS的筛选；③体外实验探讨CS作用的补体蛋白靶点及通过调节膜攻击复合物进而调节下游信号通路实现OA防治的机制；④OA小鼠模型考察CS的药效学以及证明CS通过调节补体实现OA防治的体内机制。

Osteoarthritis (OA) is a disease caused by both mechanical and biological degradation of cartilage. Alternative complement pathway plays a central role in the pathogenesis of OA. And it becomes to be a new way to attenuate OA by regulating complement system. Previously study demonstrated that chondroitin sulfate (CS) had good effect in regulating complement system and attenuating OA. However, due to different structures, sources and molecular weights, the biological activity of CS varies and the mechanism to attenuate OA was not clear. In this project, CSs with different structures and molecular weights will be prepared and in vitro experiment will be employed to select the best one. The mechanism that CS attenuates OA by regulating the complement system will be studied both in vitro and in vivo. Finally, a new strategy will be provided for attenuating OA..The main research content of this project includes: ① Prepare different CSs and characterize the CSs with different methods; ② Screen out the CS with best anti-complement activity; ③ Study the target complement protein which interact with CS and find out the signal pathway which CS regulated to realize the OA treatment in vitro; ④ Establish the OA mouse model to investigate the pharmacodynamics and demonstrate the mechanism that CS could attenuates OA by regulating complement system.