Roles of Cellular and Molecular Targets of Wear Debris in Periprosthetic Osteolysis

Wear-generated particulate debris is the main cause of initiating this destructive process. We present recent advances in understanding of how wear debris causes osteolysis in the aspect of cellular and molecular biological levels. Macrophages, the most important cellular target for wear debris, respond to particle challenge in two distinct ways of pro-inflammatory signaling and inhibition of the protective actions of anti-osteoclastogenic cytokines, finally leading to suppression of osteogenic activity as well as increased osteoclast activity. At a molecular level, such alterations of cellular activities occur through MAP kinase, transcription factors including NF-κB, Wnt/β-catenin signaling and cytokine signaling cascades in various kinds of cells.