PPARγ Attenuates Interleukin‐1β‐Induced Cell Apoptosis by Inhibiting NOX2/ROS/p38MAPK Activation in Osteoarthritis Chondrocytes

Reactive oxygen species (ROS) induced by extracellular cytokines trigger the expression of inflammatory mediators in osteoarthritis (OA) chondrocyte. Peroxisome proliferator-activated receptor gamma (PPAR γ ) exerts an anti-inflammatory effect. The aim of this study was to elucidate the role of PPAR γ in interleukin-1 β - (IL-1 β -) induced cyclooxygenase-2 (COX-2) and prostaglandin E 2 (PGE 2 ) expression through ROS generation in OA chondrocytes.Methods IL-1 β -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 β -induced COX-2 and PGE2 expression was investigated using pharmacologic inhibitors and further analyzed by western blotting. Activation of PPAR γ was performed by using a pharmacologic agonist and was analyzed by western blotting.Results IL-1 β -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 γ 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 γ .Conclusion In OA chondrocytes, IL-1 β induced COX-2 and PGE 2 expression via activation of NOX2, which led to ROS production and MAPK activation. The activation of PPAR γ exerted protective roles in the pathogenesis of OA.