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The inhibition of RANKL expression in fibroblasts attenuate CoCr particles induced aseptic prosthesis loosening via the MyD88-independent TLR signaling pathway

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, Niandong, Deng, Lianfu, Song, Weidong, Zhang, Xiaoling, Shen, Lei, Chen, Xiaodong
Biochemical and biophysical research communications 2018 v.503 no.2 pp. 1115-1122
Lentivirus, Toll-like receptors, bone resorption, chromium, cobalt, fibroblasts, friction, hips, osteoarthritis, patients, prostheses, signal transduction
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.