AMP-activated protein kinase (AMPK) positively regulates osteoblast differentiation via induction of Dlx5-dependent Runx2 expression in MC3T3E1 cells

Won Gu Jang; Eun Jung Kim; Kkot-Nim Lee; Hye-Ju Son; Jeong-Tae Koh

doi:10.1016/j.bbrc.2010.12.099

AMP-activated protein kinase (AMPK) positively regulates osteoblast differentiation via induction of Dlx5-dependent Runx2 expression in MC3T3E1 cells

Biochem Biophys Res Commun. 2011 Jan 28;404(4):1004-9. doi: 10.1016/j.bbrc.2010.12.099. Epub 2010 Dec 25.

Authors

Won Gu Jang¹, Eun Jung Kim, Kkot-Nim Lee, Hye-Ju Son, Jeong-Tae Koh

Affiliation

¹ Department of Pharmacology and Dental Therapeutics and BK21, School of Dentistry, Chonnam National University, Gwangju 500-757, Republic of Korea. [email protected]

PMID: 21187071
DOI: 10.1016/j.bbrc.2010.12.099

Abstract

This study examined the role of AMPK activation in osteoblast differentiation and the underlining mechanism. An AMPK activator (AICAR or metformin) stimulated osteoblast differentiation with increases in ALP and OC protein production as well as the induction of AMPK phosphorylation in MC3T3E1 cells. In addition, metformin induced the phosphorylation of Smad1/5/8 and expression of Dlx5 and Runx2, whereas compound C or dominant negative AMPK inhibited these effects. Transient transfection studies also showed that metformin increased the BRE-Luc and Runx2-Luc activities, which were inhibited by DN-AMPK or compound C. Down-regulation of Dlx5 expression by siRNA suppressed metformin-induced Runx2 expression. These results suggest that the activation of AMPK stimulates osteoblast differentiation via the regulation of Smad1/5/8-Dlx5-Runx2 signaling pathway.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

3T3 Cells
AMP-Activated Protein Kinase Kinases
Aminoimidazole Carboxamide / analogs & derivatives
Aminoimidazole Carboxamide / pharmacology
Animals
Cell Differentiation / drug effects
Cell Differentiation / genetics*
Core Binding Factor Alpha 1 Subunit / genetics*
Homeodomain Proteins / genetics
Homeodomain Proteins / metabolism*
Metformin / pharmacology
Mice
Osteoblasts / cytology*
Osteoblasts / drug effects
Osteoblasts / enzymology
Protein Kinases / genetics
Protein Kinases / metabolism*
RNA, Small Interfering / genetics
Ribonucleotides / pharmacology
Smad1 Protein / metabolism
Smad5 Protein / metabolism
Smad8 Protein / metabolism
Transcription, Genetic*

Substances

Core Binding Factor Alpha 1 Subunit
Dlx5 protein, mouse
Homeodomain Proteins
RNA, Small Interfering
Ribonucleotides
Runx2 protein, mouse
Smad1 Protein
Smad1 protein, mouse
Smad5 Protein
Smad5 protein, mouse
Smad8 Protein
Smad9 protein, mouse
Aminoimidazole Carboxamide
Metformin
Protein Kinases
AMP-Activated Protein Kinase Kinases
AICA ribonucleotide