Ppar Gamma Attenuates Interleukin-1 Beta-Induced Cell Apoptosis By Inhibiting Nox2/Ros/P38mapk Activation In Osteoarthritis Chondrocytes

Introduction. Reactive oxygen species (ROS) induced by extracellular cytokines trigger the expression of inflammatory mediators in osteoarthritis (OA) chondrocyte. Peroxisome proliferator-activated receptor gamma (PPAR gamma) exerts an anti-inflammatory effect. The aim of this study was to elucidate the role of PPAR gamma in interleukin-1 beta- (IL-1 beta-) induced cyclooxygenase-2 (COX-2) and prostaglandin E-2 (PGE(2)) expression through ROS generation in OA chondrocytes. Methods. IL-1 beta-induced ROS generation and chondrocyte apoptosis were determined by flow cytometry. Contents of NADPH oxidase (NOX), caspase-3, and caspase-9 were evaluated by biochemical detection. The involvement of NOX2 and mitogen-activated protein kinases (MAPKs) in IL-1 beta-induced COX-2 and PGE2 expression was investigated using pharmacologic inhibitors and further analyzed by western blotting. Activation of PPAR gamma was performed by using a pharmacologic agonist and was analyzed by western blotting. Results. IL-1 beta-induced COX-2 and PGE(2) expression was mediated through NOX2 activation/ROS production, which could be attenuated by N-acetylcysteine (NAC; a scavenger of ROS), GW1929 (PPAR gamma agonist), DPI (diphenyleneiodonium chloride, NOX2 inhibitor), SB203580 (p38MAPK inhibitor), PD98059 (extracellular signal-regulated kinase, ERK inhibitor), and SP600125 (c-Jun N-terminal kinase, JNK inhibitor). ROS activated p38MAPK to enter the nucleus, which was attenuated by PPAR gamma. Conclusion. In OA chondrocytes, IL-1 beta induced COX-2 and PGE(2) expression via activation of NOX2, which led to ROS production and MAPK activation. The activation of PPAR gamma exerted protective roles in the pathogenesis of OA.