Arsenic inhibits the adipogenic differentiation of mesenchymal stem cells by down-regulating peroxisome proliferator-activated receptor gamma and CCAAT enhancer-binding proteins

Arsenic remains a top environmental concern in the United States as well as worldwide because of its global existence and serious health impacts. Apoptotic effect of arsenic in human mesenchymal stem cells (hMSCs) has been identified in our previous study; the effects of arsenic on hMSCs remain largely unknown. Here, we report that arsenic inhibits the adipogenic differentiation of human mesenchymal stem cells (hMSCs). Arsenic reduced the formation of lipid droplets and the expression of adipogenesis-related proteins, such as CCAAT enhancer binding protein-(C/EBPs), peroxisome proliferator-activated receptor-gamma (PPAR-gamma), and adipocyte fatty acid-binding protein aP2 (aP2). Arsenic mediates this process by sustaining PPAR-gamma activity. In addition, inhibition of PPAR-gamma activity with T0070907 and up-regulation with its agonist troglitazone, showed the direct association of PPAR-gamma and arsenic-mediated inhibition of differentiating hMSCs. Taken together, these results indicate that arsenic inhibits adipogenic differentiation through PPAR-gamma pathway and suggest a novel inhibitory effect of arsenic on adipogenic differentiation in hMSCs. Crown Copyright (C) 2012 Published by Elsevier Ltd. All rights reserved.