MST1 knockdown inhibits osteoarthritis progression through Parkin‐mediated mitophagy and Nrf2/NF‐κB signalling pathway

Abstract Osteoarthritis (OA) is a complicated disease that involves apoptosis and mitophagy. MST1 is a pro‐apoptotic factor. Hence, decreasing its expression plays an anti‐apoptotic effect. This study aims to investigate the protective effect of MST1 inhibition on OA and the underlying processes. Immunofluorescence (IF) was used to detect MST1 expression in cartilage tissue. Western Blot, ELISA and IF were used to analyse the expression of inflammation, extracellular matrix (ECM) degradation, apoptosis and mitophagy‐associated proteins. MST1 expression in chondrocytes was inhibited using siRNA and shRNA in vitro and in vivo. Haematoxylin–Eosin, Safranin O‐Fast Green and alcian blue staining were used to evaluate the therapeutic effect of inhibiting MST1. This study discovered that the expression of MST1 was higher in OA patients. Inhibition of MST1 reduced inflammation, ECM degradation and apoptosis and enhanced mitophagy in vitro. MST1 inhibition slows OA progression in vivo. Inhibiting MST1 suppressed apoptosis, inflammation and ECM degradation via promoting Parkin‐mediated mitophagy and the Nrf2‐NF‐κB axis. The results suggest that MST1 is a possible therapeutic target for the treatment of osteoarthritis as its inhibition delays the progression of OA through the Nrf2‐NF‐κB axis and mitophagy.