15-Hydroxyprostaglandin Dehydrogenase Is Associated with the Troglitazone-Induced Promotion of Adipocyte Differentiation in Human

Abstract － Adipocyte differentiation in human bone marrow mesenchymal stem cells (hBM-MSCs) is not as efficient as that in murine pre-adipocytes when induced by adipogenic agents including insulin, dexa-methasone, and 3-isobutyl-1-methylxanthine (IDX condition). Therefore, the promotion of adipocyte dif-ferentiation in hBM-MSCs has been used as a cell culture model to evaluate insulin sensitivity for anti-diabetic drugs. In hBM-MSCs, PPARγ agonists or sulfonylurea anti-diabetic drugs have been added to IDX conditions to promote adipocyte differentiation. Here we show that troglitazone, a peroxisome proliferator-activated receptor-gamma (PPARγ) agonist, significantly reduced the levels of anti-adipogenic PGE2 in IDX-conditioned hBM-MSC culture supernatants when compared to PGE2 levels in the absence of PPARγ agonist. However, there was no difference in the mRNA levels of cyclooxygenases (COXs) and the activities of COXs and prostaglandin synthases during adipocyte differentiation in hBM-MSCs with or without troglitazone. In hBM-MSCs, troglitazone significantly increased the mRNA level of 15-hydroxyprostaglandin dehydrogenase (HPGD) which can act to decrease PGE2 levels in culture. These results suggest that the role of PPARγ activation in promoting adipocyte differentiation in hBM-MSCs is to reduce anti-adipogenic PGE2 levels through the up-regulation of HPGD expression