Although peroxisome proliferator activated receptor (PPAR)_ remains a critical regulator of preadipocyte differentiation, new roles have been discovered in inflammation, bone morphogenesis, endothelial function, cancer, longevity and atherosclerosis. Despite the demonstration of PPAR expression in chondrocytes, its role and the pathways affecting its expression and activity in chondrocytes remain largely unknown. We investigated the effects of PPAR activation on chondrocyte differentiation and its participation in chondrocyte lipid metabolism. PPAR2 expression is highly regulated during chondrocyte differentiation in vivo and in vitro PPAR activation with troglitazone resulted in increased Indian hedgehog expression and reduced collagen X expression, confirming previously described roles in the inhibition of differentiation. However, the major effect of PPAR2 in chondrocytes appears to be on lipid metabolism. During differentiation chondrocytes increase expression of the lipid-associated metabolizing protein, Lpl, which is accompanied by increased gene expression of PPAR. PPAR expression is suppressed by p38 activity, but requires GSK-3 activity. Furthermore, Lpl expression is regulated by p38 and GSK-3 signalling. This is the first study demonstrating a relationship between PPAR2 expression and chondrocyte lipid metabolism and its regulation by p38 and GSK-3 signalling
