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Human mesenchymal stem cell differentiation to the osteogenic or adipogenic lineage is regulated by AMP‐activated protein kinase
Author(s) -
Kim EungKyun,
Lim Seyoung,
Park JiMan,
Seo Jeong Kon,
Kim Jae Ho,
Kim Kyong Tai,
Ryu Sung Ho,
Suh PannGhill
Publication year - 2012
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.22892
Subject(s) - ampk , microbiology and biotechnology , protein kinase a , gene knockdown , adipogenesis , chemistry , runx2 , mesenchymal stem cell , osteocalcin , cellular differentiation , amp activated protein kinase , osteoblast , phosphorylation , alkaline phosphatase , biology , in vitro , biochemistry , apoptosis , gene , enzyme
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. © 2011 Wiley Periodicals, Inc.