PPAR agonist protects against osteoarthritis by activating AKT/mTOR signaling pathway-mediated autophagy

Osteoarthritis (OA) is the most prevalent degenerative joint disease, and PPARs are involved in its pathogenesis; however, the specific mechanisms by which changes in PPAR delta impact the OA pathogenesis yet to be discovered. The purpose of this study was to ascertain how PPAR delta affects the onset and development of OA. In vitro, we found that PPAR delta activation ameliorated apoptosis and extracellular matrix (ECM) degradation in OA chondrocytes stimulated by IL-1 beta. In addition, PPAR delta activation may modulate AKT/mTOR signaling to partially regulate chondrocyte autophagy and apoptosis. In vivo, injection of PPAR delta agonist into the articular cavity improved ECM degradation, apoptosis and autophagy in rats OA models generated by destabilization medial meniscus (DMM), eventually delayed degeneration of articular cartilage. Thus, targeting PPAR delta for OA treatment may be a possibility.