RIPK3在磨损颗粒激活巨噬细胞PRRs/NLRP3信号通路引起人工关节无菌性松动中的作用机制  

Mechanism of RIPK3 in activation of PRRs/NLRP3 signaling pathway in macrophages induced by wear particles in aseptic joint loosening

作　　者：彭芃 傅媛 邱俊雄 李仕勋 李长川[1] 邝满源 房桂彬 林思鹏 丁悦[1] PENG Peng;FU Yuan;QIU JunXiong;LI ShiXun;LI ChangChuan;KUANG ManYuan;FANG GuiBin;LIN SiPeng;DING Yue(Department of Orthopaedics,Sun Yixian Memorial Hospital,Sun Yat-sen University,Guangzhou 510120,China)

机构地区：[1]中山大学孙逸仙纪念医院骨外科,广州510120

出　　处：《中国科学：生命科学》2020年第10期1121-1131,共11页Scientia Sinica(Vitae)

基　　金：国家自然科学基金(批准号:81672186)资助。

摘　　要：人工关节置换术是治疗各种终末期骨关节疾病及部分骨肿瘤疾病的最有效手段,但人工关节假体的使用寿命有限.无菌性松动是限制人工关节假体远期使用寿命的主要原因,其中磨损颗粒激活巨噬细胞产生促炎因子导致的假体周围骨溶解被认为是无菌性松动发生的最重要因素.磨损颗粒能激活巨噬细胞的模式识别受体(pattern recognition receptors,PRRs)从而产生TNF-α和IL-1β等促炎因子,诱发假体周围骨溶解.本文在之前研究的基础上发现,在抑制RIPK3(receptor-interacting protein kinase 3)基因的小鼠巨噬细胞中,磨损颗粒诱导产生的促炎因子表达量显著下调,且NLRP3炎性小体组装受限.同时发现,注射靶向抑制RIPK3慢病毒的小鼠颅骨溶解效应减弱.本研究表明,RIPK3在磨损颗粒激活巨噬细胞PRRs/NLRP3信号通路引起炎症反应中起正性调控作用.Arthroplasty is the most effective method for treating end-stage bone and joint disease in the world. However, the artificial jointprosthesis has a limited service life. It is known that wear particles could stimulate macrophages to produce proinflammatorycytokine, which activates the osteoclasts around the prosthesis, and play the most important role in aseptic loosening. The particlescan activate pattern recognition receptors (PRRs) of macrophages to produce pro-inflammatory factors such as TNF-α and IL-1β, andinduce osteolysis around the prosthesis. Based on previous research, we found that in mouse macrophages with the RIPK3 geneinhibited, the expression of proinflammatory factors induced by wear particles was significantly reduced, and the assembly of NLRP3inflammatory bodies was limited. At the same time, it was found that the effects of cranium lysis were weakened in mice injected withlentivirus targeting to inhibit RIPK3. This study shows that RIPK3 plays a positive regulatory role in the inflammatory responsecaused by wear particles activating macrophage PRRs/NLRP3 signaling pathway.

关 键 词：RIPK3 NLRP3 人工关节置换 假体无菌性松动 巨噬细胞 

分 类 号：R687.4[医药卫生—骨科学]