人工关节置换术是治疗终末期骨关节疾病最有效的方法，全球每年有超过100万套的关节假体被植入，但该手术10年后有高达10%的病例会因假体无菌性松动而不得不进行复杂而高风险的人工关节翻修术，目前却无有效的方法来防治这一并发症。本人在德国留学期间及回国后的国家自然基金资助下所进行的研究表明：来源于假体的磨损颗粒通过TLR经典激活巨噬细胞，所产生的前炎症因子可进一步激活破骨细胞引起假体旁骨溶解，这是导致人工关节无菌性松动的主要原因。但哪些因子可调控磨损颗粒激活巨噬细胞TLR信号通路目前尚无文献报道。本研究将在以往的基础上，通过体内、外实验探讨核孤儿受体SHP (small heterodimer partner）这一负调控靶点在磨损颗粒启动TLR经典激活巨噬细胞通路中的作用，为明确人工关节无菌性松动的分子机制提供直接实验依据，并为防治人工关节无菌性松动开辟新的思路。

Artificial joint replacement is one of the most commonly performed and successful orthopedic procedures, more than 1 million arthroplasties are performed annually worldwide. However, periprosthetic osteolysis and subsequent aseptic joint loosening occur in about 10% of patients after 10 years of the initial surgery. To date, there is no approved conservative therapy to prevent or inhibit periprosthetic osteolysis. Our previous study showed that wear particles could stimulate macrophages via TLR signal pathway to release inflammatory cytokines, which stimulate osteoclasts to evoke periprosthetic osteolysis. However, there is no report on what factors could regulate the TLR signal pathway in this field. This study focuses on SHP as an intrinsic negative regulator of TLR-triggered inflammatory responses in aseptic loosening. This study aims to provide direct experimental basis to confirm the molecular mechanism of aseptic joint loosening, and try to explore newly developing therapeutic method.