Autophagy Involvement in Aseptic ioosening of Arthroplasty Components

Aseptic loosening, the most common cause of arthroplasty component failure, is due to implant wear and subsequent release of biomaterial wear particles to the bone microenvironment, leading to a chronic inflammatory response. Autophagy, a cell-cleaning process allowing the degradation of damaged material, can be upregulated in response to various stresses in which it acts primarily as a survival mechanism. In addition to the classic role of autophagy in the degradation pathway, autophagy can be involved in some secretion processes. Autophagy seems to be triggered by the presence of wear debris in the 3 main cell types involved in aseptic loosening, i.e., osteocytes, osteoblasts, and macrophages. Autophagy can mediate the secretion of proinflammatory cytokines such as interleukin (IL)-6 and IL-8 or the danger signal protein HMGB1 (high mobility group box 1). All of these proteins have been implicated in the pathogenesis of aseptic loosening. Recent studies using animal models have demonstrated that autophagy inhibition can decrease the severity of osteolysis, suggesting that transient and local autophagy modulation could be a potential therapeutic option to prevent wear debris-induced osteolysis.