Chemerin/ChemR23 signaling mediates the effects of ultra-high molecular weight polyethylene wear particles on the balance between osteoblast and osteoclast differentiation

BACKGROUND: Ultra-high molecular weight polyethylene (UHMWPE) is one of the favored materials for total joint replacement, but its wear particles cause osteolysis. This study aims to elucidate the signaling that mediates the effects of UHMWPE particles on bone cells. METHODS: RAW264.7 and MC3T3-E1 cells were treated with UHMWPE particles. Chemerin/ChemR23 signaling was manipulated by either overexpressing Rarres2 and Cmklr1 or silencing Cmklr1. The osteoblast and osteoclast differentiation was evaluated by Alizarin red and TRAP staining, respectively. The expression of osteogenic and osteoclastogenic markers was assessed with quantitative real time PCR and western blot. RESULTS: UHMWPE particles upregulated the expression of Rarres2 and Cmklr1 in both osteoblast and osteoclast precursor cells. UHMWPE particles induced osteoclast differentiation while inhibited osteoblast differentiation, and this effect was abrogated by silencing Cmklr1 but augmented by the overexpression of Rarres2 and Cmklr1. Similarly, the expression of osteogenic marker genes was inhibited while that of osteoclastogenic marker genes was activated by UHMWPE particles, and this effect was abolished by silencing Cmklr1 and enhanced by Rarres2 and Cmklr1 overexpression. CONCLUSIONS: These results demonstrated that chemerin/ChemR23 signaling plays a central role in the effects of UHMWPE particles on the balance of osteogenic and osteoclastogenic differentiation, which changes the course of bone remodeling and eventually results in osteolysis.