Erythropoietin inhibits adipogenesis of mouse bone marrow mesenchymal stem cells by activating ERK and p38 MAPK

AIM:To explore the role of erythropoietin (EPO) in the differentiation of mouse bone marrow-derived mesenchymal stem cells (MSCs) into adipocytes. METHODS:The mouse MSCs were cultured using routine methods. The cells were induced to differentiate by the cocktail medium containing 3-isobutyl-1-methylxanthine, insulin and dexamethasone, and the cells in the experiment group were treated with EPO. On the 20th day of induced differentiation, the cells were detected by oil red O staining. The mRNA expression of peroxisome proliferator-activated receptor γ (PPARγ), CCAAT/enhancer-binding protein α (C/EBPα), fatty acid binding protien 4 (FABP4) and adiponectin were determined by real-time fluorescence quantitative PCR. The phosphorylation levels of PPARγ, extracellular signal-regulated kinase (ERK) and p38 mitogen-activated protein kinase (p38 MAPK) were measured by Western blotting. MTT assay was adopted to detect the proliferation. RESULTS:During adipogenic induction, EPO decreased lipid accumulation, and inhibited the adipogenic differentiation of MSCs without cytotoxicity. The mRNA expression of PPARγ, C/EBPα, FABP4 and adiponectin was significantly inhibited in induced cells. Moreover, EPO enhanced the activity of both p38 MAPK and ERK, and increased PPARγ phosphorylation. CONCLUSION: EPO significantly inhibits differentiation of mouse bone marrow-derived MSCs into adipocytes in vitro via reducing the mRNA expression of PPARγ, C/EBPα, FABP4 and adiponectin, which may be mediated by the p38 MAPK and ERK signaling pathways.