Open AccessPPARγ2 expression in growth plate chondrocytes is regulated by p38 and GSK‐3
Author(s) -
Stanton LeeAnne,
Li Jennifer Ruizhe,
Beier Frank
Publication year - 2010
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/j.1582-4934.2008.00396.x
Subject(s) - chondrocyte , microbiology and biotechnology , peroxisome proliferator activated receptor , lipid metabolism , adipogenesis , biology , p38 mitogen activated protein kinases , troglitazone , indian hedgehog , cellular differentiation , signal transduction , endocrinology , chemistry , receptor , medicine , hedgehog signaling pathway , in vitro , mapk/erk pathway , biochemistry , gene , mesenchymal stem cell
Although peroxisome proliferator activated receptor (PPAR)γ 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 PPARγ expression in chondrocytes, its role and the pathways affecting its expression and activity in chondrocytes remain largely unknown. We investigated the effects of PPARγ activation on chondrocyte differentiation and its participation in chondrocyte lipid metabolism. PPARγ2 expression is highly regulated during chondrocyte differentiation in vivo and in vitro PPARγ 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 PPARγ2 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 γ. PPAR γ 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 PPARγ2 expression and chondrocyte lipid metabolism and its regulation by p38 and GSK‐3 signalling .