title: AMP-activated protein kinase (AMPK) positively regulates osteoblast differentiation via induction of Dlx5-dependent Runx2 expression in MC3T3E1 cells.
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.
authors.affiliation: Department of Pharmacology and Dental Therapeutics and BK21, School of Dentistry, Chonnam National University, Gwangju 500-757, Republic of Korea. jangwg@chonnam.ac.kr
authors.forename: Won Gu
authors.initials: WG
authors.lastname: Jang
authors.forename: Eun Jung
authors.initials: EJ
authors.lastname: Kim
authors.forename: Kkot-Nim
authors.initials: KN
authors.lastname: Lee
authors.forename: Hye-Ju
authors.initials: HJ
authors.lastname: Son
authors.forename: Jeong-Tae
authors.initials: JT
authors.lastname: Koh
mesh_terms: D016475:3T3 Cells; D000091162:AMP-Activated Protein Kinase Kinases; D000620:Aminoimidazole Carboxamide / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics*; D050659:Core Binding Factor Alpha 1 Subunit / Q000235:genetics*; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D008687:Metformin / Q000494:pharmacology; D051379:Mice; D010006:Osteoblasts / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D012265:Ribonucleotides / Q000494:pharmacology; D051898:Smad1 Protein / Q000378:metabolism; D051902:Smad5 Protein / Q000378:metabolism; D051904:Smad8 Protein / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D050659:Core Binding Factor Alpha 1 Subunit; C501120:Dlx5 protein, mouse; D018398:Homeodomain Proteins; D034741:RNA, Small Interfering; D012265:Ribonucleotides; C493716:Runx2 protein, mouse; D051898:Smad1 Protein; C497401:Smad1 protein, mouse; D051902:Smad5 Protein; C497798:Smad5 protein, mouse; D051904:Smad8 Protein; C491621:Smad9 protein, mouse; D000620:Aminoimidazole Carboxamide; D008687:Metformin; D011494:Protein Kinases; D000091162:AMP-Activated Protein Kinase Kinases; C031143:AICA ribonucleotide