Peroxiredoxin 4 inhibits IL-1β-induced chondrocyte apoptosis via PI3K/AKT signaling

BackgroundChondrocytes apoptosis induced by reactive oxygen species (ROS) plays a critical role in the pathogenesis of osteoarthritis (OA). Peroxiredoxin 4 (PRDX4), a member of the PRDX family, is essential for removing metabolic free radicals and reducing intracellular ROS. In this study, we sought to investigate the roles of PRDX4 on interleukin 1β (IL-1β)-induced chondrocyte apoptosis.MethodsPrimary chondrocytes were isolated from the articular cartilage of Sprague-Dawley rats, infected with PRDX4 overexpressing lentivirus and treated with IL-1β (10 ng/mL). Cell apoptosis and ROS production identified by flow cytometry. Protein expression levels was evaluated by Western blotting analysis. Nitric oxide (NO) production and Caspase-3/9 activation were assessed by the Griess reaction method and colorimetric assay kit, respectively.ResultsPRDX4 overexpression in chondrocytes significantly decreased IL-1β-induced apoptosis. It also reversed the activity of IL-1β that increased ROS and NO production. PRDX4 overexpression reversed the activity of IL-1β that reduced the levels of Bcl-2, p-AKT and p-PRAS40, as well as increased Bax levels and Caspase-3/9 activation. More importantly, pre-treated with AKT inhibitor (AZD5363) significantly reduced the protective effects of PRDX4.ConclusionsOur data demonstrated that the regulatory effects of PRDX4 on IL-1β-induced chondrocyte apoptosis can be partially attributed to phosphatidylinositol 3-kinase/AKT signaling. These results indicate that PRDX4 might play a protective role in OA cartilage degeneration.