Egr‐1 mediates the suppressive effect of IL‐1 on PPARg expression in human OA chondrocytes

Background Peroxisome proliferator‐activated receptor gamma (PPARg) is a ligand activated transcription factor. Several lines of evidence indicate that PPARg have protective effects in osteoarthritis (OA). We have previously shown that IL‐1 down‐regulated PPARg expression in OA chondrocytes. In the present study we will investigate the mechanisms underlying this effect of IL‐1. Methods Chondrocytes were stimulated with IL‐1, and the level of PPARg and Egr‐1 protein and mRNA were evaluated using WB and Real Time‐RT‐PCR, respectively. The PPARg promoter activity was analyzed in transient transfection experiments. Egr‐1 recruitment to the PPARg promoter was evaluated using ChIP assays. Small interfering RNA (siRNA) approaches were used to silence Egr‐1 expression. Results We demonstrated that the suppressive effect of IL‐1 on PPARg expression requires de novo protein synthesis. ChIP analyses revealed that IL‐1 induced Egr‐1 recruitment at the PPARg promoter. IL‐1 inhibited the activity of PPARg promoter and overexpression of Egr‐1 potentiated the inhibitory effect of IL‐1, suggesting that Egr‐1 may mediate the suppressive effect of IL‐1. Finally, Egr‐1 silencing with siRNA blocked IL‐1‐mediated down‐regulation of PPARg expression. Conclusion These results indicate that Egr‐1 contributes to IL‐1‐mediated down‐regulation of PPARg expression in OA chondrocytes.