ERRα ameliorates osteoarthritis by inhibiting chondrocyte pyroptosis via targeting NF-κBp65.

Osteoarthritis (OA) is a metabolic disorder that remains difficult to cure due to its complex pathogenesis. ERRα plays a broad role in cellular metabolism and inflammation; however, whether ERRα can also ameliorate OA through the regulation of chondrocyte pyroptosis remains unclear. The present study aimed to evaluate the potential role and underlying mechanisms of ERRα in OA. ERRα expression was found to be downregulated in patients with OA, OA rats, and OA cells. In both in vivo and in vitro experiments, ERRα overexpression inhibited chondrocyte pyroptosis, promoted anabolic activity, suppressed catabolic processes, and attenuated inflammation, whereas ERRα knockdown exacerbated chondrocyte pyroptosis, impaired anabolism, enhanced catabolism, and aggravated inflammatory responses. Furthermore, chromatin immunoprecipitation and dual-luciferase reporter assays demonstrated that ERRα binds to the p65 promoter and suppresses the NF-κB signaling pathway. These findings identified ERRα as a potential therapeutic target, whereby ERRα alleviates OA by regulating chondrocyte metabolism and injury through inhibition of chondrocyte pyroptosis.