Apelin‐13 alleviates osteoclast formation and osteolysis through Nrf2‐pyroptosis pathway

Abstract

AbstractWear particle‐induced periprosthetic osteolysis is the key to aseptic loosening after artificial joint replacement. Osteoclastogenesis plays a central role in this process. Apelin‐13 is a member of the adipokine family with anti‐inflammatory effects. Here, we report that apelin‐13 alleviates RANKL‐mediated osteoclast differentiation and titanium particle‐induced osteolysis in mouse calvaria. Mechanistically, apelin‐13 inhibits NLRP3 inflammasome‐mediated pyroptosis by activating the nuclear factor erythroid 2‐related factor 2 (Nrf2) pathway. In summary, apelin‐13 is expected to be a potential drug for relieving aseptic osteolysis.Research Highlights This study reveals the molecular mechanism by which apelin‐13 inhibits NLRP3 inflammasome activation and pyroptosis by promoting Nrf2. This study confirms that apelin‐13 alleviates osteoclast activation by inhibiting pyroptosis. In vivo studies further confirmed that apelin‐13 alleviated mouse skull osteolysis by inhibiting the activation of NLRP3 inflammasome.