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

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.

• Authors: Eung-Kyun Kim, Seyoung Lim, Ji-Man Park, Jeong Kon Seo, Jae Ho Kim, Kyong Tai Kim, Sung Ho Ryu, Pann-Ghill Suh
• Journal: Journal of cellular physiology (J Cell Physiol) Vol. 227 Issue 4 Pg. 1680-7 (Apr 2012) ISSN: 1097-4652 [Electronic] United States
• PMID: 21678424 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 Wiley Periodicals, Inc.

Chemical References

• Protein Kinase Inhibitors
• Pyrazoles
• Pyrimidines
• RNA, Small Interfering
• dorsomorphin
• AMP-Activated Protein Kinases
• PRKAA1 protein, human

Topics

• AMP-Activated Protein Kinases (antagonists & inhibitors, genetics, metabolism)
• Adipogenesis (drug effects, physiology)
• Base Sequence
• Cell Differentiation (drug effects, physiology)
• Cells, Cultured
• Gene Knockdown Techniques
• Humans
• MAP Kinase Signaling System
• Mesenchymal Stem Cells (cytology, drug effects, enzymology)
• Osteogenesis (drug effects, physiology)
• Phosphorylation
• Protein Kinase Inhibitors (pharmacology)
• Pyrazoles (pharmacology)
• Pyrimidines (pharmacology)
• RNA, Small Interfering (genetics)