骨性关节炎（OA）是中老年人常见多发病，目前缺乏无创、安全且有效的治疗手段。既往研究表明关节软骨细胞自噬功能障碍是导致OA进展的重要因素。本课题组研究发现低强度脉冲超声波（LIPUS）能够促进OA软骨细胞自噬，上调自噬相关蛋白ATG5，并且阻断自噬后LIPUS抑制细胞外基质丢失的作用就被显著削弱了。据此，我们提出LIPUS可能通过促进ATG5调节自噬影响OA软骨细胞功能，进而延缓OA关节软骨退变。本项目拟在前期工作的基础上，利用可诱导的成年期软骨细胞特异性敲除ATG5遗传小鼠模型，结合细胞和分子生物学研究手段，进一步明确LIPUS通过ATG5调控软骨细胞自噬在OA中的作用并探讨相关分子机制。本研究探讨了LIPUS通过自噬调控软骨细胞功能的新机制，将为LIPUS治疗OA的提供理论依据，为进一步研究LIPUS在OA中的作用奠定实验基础。

Osteoarthritis (OA) is the most common joint disease in the elderly, which is lack of effective and noninvasive treatments. Previous studies demonstrated that the autophagy dysfunction of articular chondrocytes is essential to the development of OA. In our study, we found that low-intensity pulsed ultrasound (LIPUS) induced autophagy and the expression of ATG5 in OA chondrocytes. In addition，the presence of autophagy inhibitor negated the positive effects of LIPUS on cartilage matrix. Our previous findings suggested that LIPUS protects articular cartilage from degeneration by promoting chondrocyte autophagy, and this effect is exerted through the up-regulation of ATG5.In this study, we will use the genetic mouse model which conditional knock-out ATG5 in chondrocytes to further clarify the function of LIPUS promoting chondrocyte autophagy via ATG5 in OA and explore the mechanisms. This study will provide a theoretical basis for LIPUS in the treatment of OA.