The inhibition of RANKL expression in fibroblasts attenuate CoCr particles induced aseptic prosthesis loosening via the MyD88-independent TLR signaling pathway
The inhibition of RANKL expression in fibroblasts attenuate CoCr particles induced aseptic prosthesis loosening via the MyD88-independent TLR signaling pathway
复制标题
成纤维细胞中 RANKL 表达的抑制可通过不依赖 MyD88 的 TLR 信号通路减弱 CoCr 颗粒引起的无菌假体松动
DOI：
10.1016/j.bbrc.2018.06.128
复制
发表时间：
2018
影响因子：
3.1
通讯作者：
Chen Xiaodong
中科院分区：
文献类型：
--
作者：
Li De;Wang Hui;Li Zhuokai;Wang Chenglong;Xiao Fei;Gao Yuan;Zhang Xiang;Wang Peng;Peng Jianping;Cai Guiquan;Zuo Bin;Shen Yun;Qi Jin;Qian Ni;ong;Deng Lianfu;Song Weidong;Zhang Xiaoling;Shen Lei;Chen Xiaodong
假体周围骨质溶解和无菌性松动主要由摩擦界面产生的磨损颗粒（Ps）引起。然而，无菌性松动发生的机制尚不清楚。因此，我们的目的是阐明髓样分化因子88（MyD 88）非依赖性Toll样受体（TLR）信号通路如何介导钴铬（CoCr）-Ps诱导的骨质溶解。我们定量了初次全髋关节置换术（THA）后金属对金属（MoM）关节面和髋关节骨关节炎（hOA）发生无菌性松动的患者中TLR、MyD 88、RANKL和炎症因子的表达水平。我们通过应用shMyD 88干扰慢病毒载体来阻断MyD 88非依赖性TLR途径，观察了用CoCr Ps攻击的成纤维细胞中RANKL、TLR和MyD 88的体外和体内水平。MoM翻修THA（rTHA）组的TLR、MyD 88、RANKL和炎症因子水平高于hOA组。我们的数据共同表明，抑制MyD 88表达可以减少体外破骨细胞生成和体内CoCr-Ps诱导的骨质溶解。我们的研究结果表明，破骨细胞的生成是由CoCr-Ps诱导的成纤维细胞中RANKL的表达促进的，MyD 88是治疗磨损Ps诱导的骨质溶解的潜在靶点。
Periprosthetic osteolysis and aseptic loosening are mainly caused by wear particles (Ps) that are generated from friction interfaces. However, the mechanisms underlying the development of aseptic loosening remain unclear. Therefore, we aimed toclarify how the myeloid differentiation factor 88 (MyD88)-independent Toll-like receptor (TLR) signaling pathway mediates cobalt and chromium (CoCr)-Ps-induced osteolysis. We quantified the expression levels of TLRs, MyD88, RANKL, and inflammatory factors in patients experiencing aseptic loosening after primary total hip arthroplasty (THA) with metal-on-metal (MoM) bearings and hip osteoarthritis (hOA). We observed the in vitro and in vivo levels of RANKL, TLRs, and MyD88 in fibroblasts challenged with CoCr Ps by applying shMyD88 interference lentivirus vectors to block the MyD88-independent TLR pathway. The levels of TLRs, MyD88, RANKL, and inflammatory factors in the revision THA (rTHA) with MoM group were higher than those in the hOA group. Our data collectively revealed that inhibiting MyD88 expression could reduce osteoclastogenesis in vitro and CoCr-Ps-induced osteolysis in vivo. Our findings suggested that osteoclastogenesis is promoted by the CoCr-Ps-induced expression of RANKL in fibroblasts and that MyD88 is a potential target in the treatment of wear Ps-induced osteolysis.