title: AMP-activated protein kinase attenuates Wnt/β-catenin signaling in human osteoblastic Saos-2 cells.
abstract: AMP-activated protein kinase (AMPK) is a key sensor of cellular energetic conditions. Recent studies suggest that AMPK affects osteoblast differentiation, although its role and mechanism are not fully understood. One of the most important signals in osteoblast differentiation is the Wnt/β-catenin pathway which induces T-cell transcription factor 1 (TCF)-dependent transcription. Using human osteoblast-like Saos-2 cells, we determined whether AMPK modulates Wnt/β-catenin signaling in osteoblasts. Chemical activators of AMPK (AICAR [5-aminoimidazole-4-carboxamide riboside], metformin) suppressed Wnt3a-induced TCF-dependent transcriptional activity. Transactivation by Wnt was potentiated by inhibiting β-catenin degradation with lithium chloride (LiCl). LiCl-induced Wnt transactivation was suppressed by addition of metformin. Metformin increased the phosphorylation of β-catenin and decreased β-catenin protein levels leading to suppression of Wnt/β-catenin signaling. Our present study showed that AMPK attenuates Wnt/β-catenin signaling by reducing β-catenin protein levels in osteoblast-like cells.
authors.affiliation: Department of Pediatrics, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba-shi, Chiba 260-8670, Japan. ttgjun@yahoo.co.jp
authors.forename: Tomozumi
authors.initials: T
authors.lastname: Takatani
authors.forename: Masanori
authors.initials: M
authors.lastname: Minagawa
authors.forename: Rieko
authors.initials: R
authors.lastname: Takatani
authors.forename: Kaori
authors.initials: K
authors.lastname: Kinoshita
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Kohno
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000818:Animals; D002460:Cell Line; D017077:Culture Media, Conditioned; D017930:Genes, Reporter; D006801:Humans; D018021:Lithium Chloride / Q000494:pharmacology; D049409:Luciferases, Firefly / Q000096:biosynthesis / Q000235:genetics; D008687:Metformin / Q000494:pharmacology; D051379:Mice; D010006:Osteoblasts / Q000378:metabolism*; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D015398:Signal Transduction; D051822:T Cell Transcription Factor 1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D015533:Transcriptional Activation; D014740:Vidarabine / Q000494:pharmacology; D051153:Wnt Proteins / Q000378:metabolism*; D060508:Wnt3 Protein; D060509:Wnt3A Protein; D051176:beta Catenin / Q000378:metabolism*
chemical_list: D017077:Culture Media, Conditioned; D051822:T Cell Transcription Factor 1; C555510:WNT3A protein, human; D051153:Wnt Proteins; D060508:Wnt3 Protein; D060509:Wnt3A Protein; C555511:Wnt3a protein, mouse; D051176:beta Catenin; D008687:Metformin; D049409:Luciferases, Firefly; D055372:AMP-Activated Protein Kinases; D014740:Vidarabine; D018021:Lithium Chloride