Serum regulates adipogenesis of mesenchymal stem cells via MEK/ERK-dependent PPARgamma 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. PPARgamma had been considered as an important molecular marker of cells undergoing adipogenic differentiation. Here, we demonstrated that expression and phosphorylation of PPARgamma could be found in bone marrow-derived MSCs cultured in expansion medium without any adipogenic additives (dexamethasone, IBMX, insulin or indomethacin). Then, PPARgamma was dephosphorylated in MSCs during the process of adipogenic differentiation. We then found that inhibition of MEK activation by specific inhibitor (PD98059) counteracted the PPARgamma expression and phosphorylation. However, expression and phosphorylation of PPARgamma 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 PPARgamma. Moreover, exposure of MSCs to higher concentration of serum induced stronger PPARgamma expression, and subsequently enhanced their adipogenesis. These data suggested that activation of the MEK/ERK signalling pathway by high serum concentration promoted PPARgamma expression and phosphorylation, and subsequently enhanced adipogenic differentiation of MSCs.
Wu
Ling
L
State Key Laboratory of Oral Diseases, West China College of Stomatology, Sichuan University, Chengdu, P. R. China.
Cai
Xiaoxiao
X
Dong
Hai
H
Jing
Wei
W
Huang
Yuanding
Y
Yang
Xingmei
X
Wu
Yao
Y
Lin
Yunfeng
Y
D050156:Adipogenesis / Q000187:drug effects; D000818:Animals; D002478:Cells, Cultured; D004789:Enzyme Activation / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D020935:MAP Kinase Signaling System / Q000187:drug effects; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D020929:Mitogen-Activated Protein Kinase Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D047495:PPAR gamma / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D044967:Serum / Q000378:metabolism*
D047495:PPAR gamma; D047428:Protein Kinase Inhibitors; D048049:Extracellular Signal-Regulated MAP Kinases; D020929:Mitogen-Activated Protein Kinase Kinases