Bag3 protects chondrocytes and alleviates osteoarthritis by restoring autophagy flux

Abstract

Objective Chondrocyte apoptosis resulting from the inhibition of autophagic flux is a significant contributor to Osteoarthritis (OA). In recent years, there has been increasing interest in the role of Bcl-2-associated athanogene 3 (Bag3) in autophagy; however, its specific contribution to the pathogenesis of knee osteoarthritis remains unclear.Methods X-ray imaging and tissue staining techniques were used to evaluate the radiographic and histomorphological features of the mouse knee joint. Western blotting was employed to analyze gene and protein expression levels in an in vitro setting. Immunofluorescence staining was utilized to identify and visualize specific proteins in the tissue samples. Knockdown and overexpression techniques were employed to manipulate the expression level of BAG3, a protein of interest. DMM (destabilization of the medial meniscus) was used to induce osteoarthritis in mice for studying the effects of Bag3 overexpression on OA development.Results The results of these experiments showed that in mouse knee OA tissue, BAG3 was upregulated compared to healthy tissue. Knockdown and overexpression experiments of BAG3 revealed a potential anti-apoptotic and autophagy-enhancing function of BAG3 in the context of osteoarthritis. CQ treatment reversed BAG3-induced chondrocyte protection under oxidative stress. Bag3 overexpression ameliorated DMM-induced OA development in mice.Conclusion Bag3 alleviates chondrocytes apoptosis by protecting autophagic flux, thereby improving OA.