Serum regulates adipogenesis of mesenchymal stem cells via MEK/ERK-dependent PPARγ expression and phosphorylation

Mesenchymal stem cells (MSCs) provide us an excellent cellular model to uncover the molecular mechanisms underlying adipogenic differentiation of adult stem cells. PPAR gamma had been considered as an important molecular marker of cells undergoing adipogenic differentiation. Here, we demonstrated that expression and phosphorylation of PPAR gamma could be found in bone marrow-derived MSCs cultured in expansion medium without any adipogenic additives (dexamethasone, IBMX, insulin or indomethacin). Then, PPAR gamma was dephosphorylated in MSCs during the process of adipogenic differentiation. We then found that inhibition of MEK activation by specific inhibitor (PD98059) counteracted the PPAR gamma expression and phosphorylation. However, expression and phosphorylation of PPAR gamma did not present in MSCs cultured in medium with lower serum concentration. When these MSCs differentiated into adipocytes, no phosphorylation could be detected to accompany the expression of PPAR gamma. Moreover, exposure of MSCs to higher concentration of serum induced stronger PPAR gamma expression, and subsequently enhanced their adipogenesis. These data suggested that activation of the MEK/ERK signalling pathway by high serum concentration promoted PPAR gamma expression and phosphorylation, and subsequently enhanced adipogenic differentiation of MSCs.