低强度脉冲超声促进BMSCs修复骨关节炎软骨的自噬调控机制研究

项目名称： 低强度脉冲超声促进BMSCs修复骨关节炎软骨的自噬调控机制研究

项目编号： No.81501941

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 夏鹏

作者单位： 南京医科大学

项目金额： 18万元

中文摘要： 骨关节炎（OA）引起的关节软骨损伤难以自我修复，骨髓间充质干细胞（BMSCs）可通过归巢分化修复软骨损伤，但由于BMSCs归巢成软骨分化具有随机性、分化率低，其临床治疗效果有限。低强度脉冲超声（LIPUS）是一种新兴、无创的物理治疗因子，可促进BMSCs体内归巢和体外成软骨分化，但其作用机制不明。我们前期研究发现，激活自噬可降低BMSCs归巢因子CXCR4的mRNA表达和II型胶原蛋白表达，应用LIPUS可降低BMSCs自噬基因Beclin1 的mRNA表达，提高CXCR4的mRNA表达和II型胶原蛋白表达，由此推测自噬调控对BMSCs归巢成软骨分化有一定的影响，LIPUS可能通过自噬调控途径促进BMSCs归巢成软骨分化。本课题拟采用自噬激活和抑制技术，并给予LIPUS干预，探讨LIPUS通过自噬调控途径促进BMSCs归巢分化修复OA软骨的作用机制，为OA的治疗提供新的思路和理论依据。

中文关键词： 低强度脉冲超声；骨关节炎；骨髓间充质干细胞；自噬；软骨

英文摘要： Osteoarthritis (OA) is difficult to be repaired if articular cartilage is damaged. Bone marrow mesenchymal stem cells(BMSCs) are used for cartilage repair through homing and chondrogenic differentiation. Due to the randomness and low efficiency of BMSCs homing and chondrogenic differentiation, the clinical treatment effect is limited. Low-intensity pulsed ultrasound(LIPUS) is a new and noninvasive physical therapy factor, which can promotes BMSCs homing in vivo and chondrogenic differentiation in vitro, but its mechanism is still unknown. Our previous study found that the activation of autophagy could decrease mRNA expression of homing related gene CXCR4 and protein expression of type-II collagen, and LIPUS could decrease mRNA expression of autophagy related gene Beclin1, increase mRNA expression of CXCR4 and protein expression of type-II collagen. We hypothesize that regulation of autophagy has an effect on homing and chondrogenic differentiation of BMSCs, and LIPUS promotes homing and chondrogenic differentiation of BMSCs through autophagy regulation. This research will adopt autophagy activation and suppression technology, and to give LIPUS intervention, in order to prove the meschanism of LIPUS promotes homing and chondrogenic differentiation of BMSCs through autophagy regulation for OA cartilage repair . This study will provide a new method and theoretical basis for the treatment of OA.

英文关键词： low-intensity pulsed ultrasound;osteoarthritis;BMSCs;autophagy;cartilage