DDX3X Activates Chondrocyte Pyroptosis to Promote Osteoarthritis Progression

The RNA-binding protein DDX3X is associated with several biological processes including inflammation and immunity. However, the role of DDX3X in the pathology of inflammation-related osteoarthritis (OA) remains unclear. This study was to explore the action of DDX3X in the progression of OA as well as the underlying mechanisms by using RNA immunoprecipitation (RIP), Immunohistochemical (IHC) and DDX3X knockout mice, etc. We found that DDX3X expression was upregulated in cartilage tissue of OA patient. The in vitro study also showed upregulation of DDX3X in the inflammatory chondrocytes stimulated by LPS. DDX3X overexpression reduced cell viability by inducing pyroptosis in chondrocytes. Knockdown of DDX3X rescued LPS-induced chondrocytes pyroptosis through regulating NLRP3 signaling. In addition, DDX3X deletion attenuates osteoarthritis in vivo. In conclusion, DDX3X promotes OA progression by regulating chondrocytes pyroptosis via the activation of NLRP3 signaling.