假体松动是关节置换术后最主要的并发症，其发生的最重要原因是磨损颗粒诱导假体周围破骨-成骨平衡的破坏，最终导致的骨溶解，但具体机制不明。最新研究表明，破骨细胞分化过程中miRNA-214表达上调，不仅可促进破骨细胞活化，还能通过外泌体靶向抑制成骨细胞功能。我们预实验结果也表明在假体松动患者的界膜中miR-214高表达，同时破骨细胞增多而成骨基因表达下降，而且在体外磨损颗粒刺激巨噬细胞分泌的外泌体中miR-214表达也上升。因此，我们假设磨损颗粒刺激巨噬细胞可增加外泌体miR-214的分泌，进而分别靶向作用于破骨细胞/成骨细胞，打破破骨-成骨的平衡，最终导致假体松动。本研究拟从细胞-组织-动物实验三个层面，阐明磨损颗粒刺激巨噬细胞分泌的外泌体miR-214调控破骨细胞/成骨细胞的作用及具体机制，从而为外泌体miRNA-214成为关节假体松动潜在的诊断标志物以和治疗载体提供新思路和科学依据。

Prosthesis loosening is the most important complication after joint arthroplasty. The most important reason is that wear particles induce the destruction of osteoclast-osteogenesis balance around the prosthesis and ultimately lead to osteolysis, but the specific mechanism is not clear. Recent studies have shown that the expression of microRNA-214 is up-regulated during osteoclast differentiation, which not only can promote the activation of osteoclasts, but also can inhibit the function of osteoblasts through exosome targeting. Our preliminary data shows that the expression of microRNA-214 is up-regulated in the interface membrane of patients with prosthesis loosening, while the number of osteoclasts was increased and the expression of osteogenesis-related genes was decreased. And the expression of miR-214 also increased in the exosomes from the supernatant of macrophages stimulated by wear particles. Therefore, we hypothesize that the stimulate of macrophages by wear particles can up-regulate the secretion of the exosomal miRNA-214, and then targeting to osteoclasts/osteoblasts respectively, breaking the balance between osteoclasts and osteoblasts, leading to prosthesis loosening. In this study, we will elucidate the role and mechanism of macrophages-derived exosomal miRNA-214 stimulated by wear particles on osteoclasts/osteoblasts from different levels. After the researches above, we hope to provide new ideas and scientific basis for the exosomeal microRNA-214 as a potential diagnostic marker and therapeutic vector for the prosthetic loosening of artificial joint.