Clearance of senescent cells by navitoclax (ABT263) rejuvenates UHMWPE-induced osteolysis.

Abstract

Periprosthetic osteolysis is the leading cause of prosthesis failure and subsequent total joint revision. Wear particles produced by prosthetic materials are the main biological factors that cause periprosthetic osteolysis. Reducing the inflammatory response induced by the phagocytosis of wear particles by macrophages, blocking the activation of osteoclastogenesis, and promoting bone regeneration are essential for preventing the aseptic loosening of prostheses. In this study, we demonstrated that cellular senescence played a vital role during the process of ultra-high molecular weight polyethylene (UHMWPE) particle-induced osteolysis. Administration of the senolytic drug navitoclax (ABT263) could eliminate senescent cells and inhibit the secretion and inflammatory state of the senescence-associated secretory phenotype (SASP). We also discovered that ABT263 inhibited the formation of osteoclasts and had a significant therapeutic effect on UHMWPE particle-induced osteolysis based on the results of UHMWPE-induced mouse cranial osteolysis. Therefore, our research provided innovative strategies and ideas for the prevention and treatment of periprosthetic osteolysis.