假体周围磨损颗粒激活破骨细胞引起的骨溶解是导致人工关节无菌性松动的主要原因，靶向抑制破骨细胞预防无菌性松动成为新近研究热点。最近研究指出，miRNAs将在破骨细胞中发挥重要的调控作用。我们前期研究结果表明，miR-363-3p有望通过MITF和ITGA5负调控破骨细胞功能，提示其可用于防治磨损颗粒诱导的骨溶解。本项目拟在此基础上，采用miRNAs沉默/过表达技术，明确miR-363-3p对破骨细胞分化、功能、基因和蛋白表达的影响；其次，采用荧光素酶及转基因细胞，通过luciferase assay技术和挽救实验，验证其作用靶基因和可能的作用机制；最后，在体内建立磨损颗粒诱导的颅骨骨溶解模型，利用miRNAs沉默技术，局部注射pre-miR-363-3p，明确miR-363-3p治疗磨损颗粒诱导的骨溶解的作用。为miR-363-3p治疗该类疾病的作用、机制及应用价值提供实验依据和方法借鉴。

Aseptic loosening is one of the most common causes of failure in artificial arthroplasty, and particle-induced osteolysis is the mainly underlying mechanism. Suppressing the differentiation and function of osteoclasts have been proven as an effective way to prevent aseptic loosening. MicroRNAs (miRs) are small non-coding RNAs that principally function in the spatiotemporal regulation of protein translation in animal cells. Recent reports about osteoclastogenesis indicated that miRs might serve as important regulators in osteoclast differentiation and function. Based on our previous research data, miR-363-3p was supposed to inhibit osteoclast differentiation and function though MITF and ITGA5, thus might serve as a potential way in the treatment of aseptic loosening. In our present research, we would firstly adopt the techniques of miRs mimics/inhibitor to testify the effects of miR-363-3p on osteoclastogenesis, bone resorption, osteoclast-related specific gene and protein expression levels; after that luciferase assay and gene over-expression techniques would be performed to explore the potential mechanisms of miR-363-3p on osteoclast; finally, we would adopt wear particles induced osteolysis skull model, synthesize and inject pre-miR-363-3p locally to evaluate the therapeutic efficacy in vivo. We aim to provide experimental basis for revealing miR-363-3p’s therapeutic effect, molecular mechanism and clinical application value.