PPAR gamma and MyoD are differentially regulated by myostatin in adipose-derived stem cells and muscle satellite cells

Myostatin (MSTN) is a secreted protein belonging to the transforming growth factor-beta (TGF-beta) family that is primarily expressed in skeletal muscle and also functions in adipocyte maturation. Studies have shown that MSTN can inhibit adipogenesis in muscle satellite cells (MSCs) but not in adipose-derived stem cells (ADSCs). However, the mechanism by which MSTN differently regulates adipogenesis in these two cell types remains unknown. Peroxisome proliferator-activated receptor-gamma (PPAR gamma) and myogenic differentiation factor (MyoD) are two key transcription factors in fat and muscle cell development that influence adipogenesis. To investigate whether MSTN differentially regulates PPAR gamma and MyoD, we analyzed PPAR gamma and MyoD expression by assessing mRNA, protein and methylation levels in ADSCs and MSCs after treatment with 100 ng/mL MSTN for 0, 24, and 48 h. PPAR gamma mRNA levels were downregulated after 24 h and upregulated after 48 h of treatment in ADSCs, whereas in MSCs, PPAR gamma levels were downregulated at both time points. MyoD expression was significantly increased in ADSCs and decreased in MSCs. PPAR gamma and MyoD protein levels were upregulated in ADSCs and downregulated in MSCs. The CpG methylation levels of the PPAR gamma and MyoD promoters were decreased in ADSCs and increased in MSCs. Therefore, this study demonstrated that the different regulatory adipogenic roles of MSTN in ADSCs and MSCs act by differentially regulating PPAR gamma and MyoD expression. (C) 2015 Elsevier Inc. All rights reserved.