Description
Nrf2, a redox regulated transcription factor, has recently been shown to play a role in cartilage integrity but the mechanism remains largely unknown. Osteoarthritis (OA) is a multifactorial disease in which focal degradation of cartilage occurs. Here, we studied whether Nrf2 exerts chondroprotective effects by suppressing the oxidative stress and apoptosis in IL-1beta stimulated human OA chondrocytes. Expression of Nrf2 and its target genes HO-1, NQO1 and SOD2 was significantly high in OA cartilage compared to normal cartilage and was also higher in damaged area compared to smooth area of OA cartilage of the same patient. Human chondrocytes treated with IL-1beta resulted in robust Nrf2/ARE reporter activity, which was inhibited by pretreatment with antioxidants indicating that Nrf2 activity was due to IL-1beta-induced ROS generation. Ectopic expression of Nrf2 significantly suppressed the IL-1beta-induced generation of ROS while Nrf2 knockdown significantly increased the basal as well as
Subject
Humans; *Apoptosis; *Apoptosis; *ERK1/2; *Nrf2; *Osteoarthritis; *Redox; Oxidative Stress; Osteoarthritis/*metabolism; NF-E2-Related Factor 2/genetics/*metabolism; Up-Regulation; MAP Kinase Signaling System; Chondrocytes/*physiology; Caspases/metabolism; Cells; Cultured; 70-kDa/metabolism; Ribosomal Protein S6 Kinases; Carboxylic Ester Hydrolases/metabolism; ets-Domain Protein Elk-1/metabolism; Interleukin-1beta/immunology; 90-kDa/metabolism