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Human mesenchymal stem cell differentiation to the osteogenic or adipogenic lineage is regulated by AMP-activated protein kinase

Title
Human mesenchymal stem cell differentiation to the osteogenic or adipogenic lineage is regulated by AMP-activated protein kinase
Authors
Kim, EKLim, SPark, JMSeo, JKKim, JHKim, KTRyu, SHSuh, PG
POSTECH Authors
Kim, KTRyu, SH
Date Issued
Jan-2012
Publisher
John WILEY
Abstract
AMP-activated protein kinase (AMPK) is an energy-sensing kinase that has recently been shown to regulate the differentiation of preadipocytes and osteoblasts. However, the role of AMPK in stem cell differentiation is largely unknown. Using in vitro culture models, the present study demonstrates that AMPK is a critical regulatory factor for osteogenic differentiation. We observed that expression and phosphorylation of AMPK were increased during osteogenesis in human adipose tissue-derived mesenchymal stem cells (hAMSC). To elucidate the role of AMPK in osteogenic differentiation, we investigated the effect of AMPK inhibition or knockdown on mineralization of hAMSC. Compound C, an AMPK inhibitor, reduced mineralized matrix deposition and suppressed the expression of osteoblast-specific genes, including alkaline phosphatase (ALP), runt-related transcription factor 2 (RUNX2), and osteocalcin (OCN). Knockdown of AMPK by shRNA-lentivirus infection also reduced osteogenesis. In addition, inhibition or knockdown of AMPK during osteogenesis inhibited ERK phosphorylation, which is required for osteogenesis. Interestingly, inhibition of AMPK induced adipogenic differentiation of hAMSC, even in osteogenic induction medium (OIM). These results provide a potential mechanism involving AMPK activation in osteogenic differentiation of hAMSC and suggest that commitment of hAMSC to osteogenic or adipogenic lineage is governed by activation or inhibition of AMPK, respectively. J. Cell. Physiol. 227: 1680-1687, 2012. (C) 2011 Wiley Periodicals, Inc.
Keywords
OSTEOBLASTIC MC3T3-E1 CELLS; BONE-MARROW; ADIPOCYTE DIFFERENTIATION; ADIPOSE-TISSUE; PROMOTES OSTEOGENESIS; SIGNALING PATHWAYS; BMP-2 EXPRESSION; RECEPTOR-GAMMA; PPAR-GAMMA; IN-VITRO
URI
http://oasis.postech.ac.kr/handle/2014.oak/16658
DOI
10.1002/JCP.22892
ISSN
0021-9541
Article Type
Article
Citation
JOURNAL OF CELLULAR PHYSIOLOGY, vol. 227, no. 4, page. 1680 - 1687, 2012-01
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류성호RYU, SUNG HO
Dept of Life Sciences
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