Autophagy Involvement in Aseptic Loosening of Arthroplasty Components.

Abstract

➤ 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.