| FHL2 mediates dexamethasone-induced mesenchymal cell differentiation into osteoblasts by activating Wnt/beta-catenin signaling-dependent Runx2 expression. | |
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MedLine Citation:
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PMID: 18653765 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The differentiation of bone marrow mesenchymal stem cells (MSCs) into osteoblasts is a crucial step in bone formation. However, the mechanisms involved in the early stages of osteogenic differentiation are not well understood. In this study, we identified FHL2, a member of the LIM-only subclass of the LIM protein superfamily, that is up-regulated during early osteoblast differentiation induced by dexamethasone in murine and human MSCs. Gain-of-function studies showed that FHL2 promotes the expression of the osteoblast transcription factor Runx2, alkaline phosphatase, type I collagen, as well as in vitro extracellular matrix mineralization in murine and human mesenchymal cells. Knocking down FHL2 using sh-RNA reduces basal and dexamethasone-induced osteoblast marker gene expression in MSCs. We demonstrate that FHL2 interacts with beta-catenin, a key player involved in bone formation induced by Wnt signaling. FHL2-beta-catenin interaction potentiates beta-catenin nuclear translocation and TCF/LEF transcription, resulting in increased Runx2 and alkaline phosphatase expression, which was inhibited by the Wnt inhibitor DKK1. Reduction of Runx2 transcriptional activity using a mutant Runx2 results in inhibition of FHL2-induced alkaline phosphatase expression in MSCs. These findings reveal that FHL2 acts as an endogenous activator of mesenchymal cell differentiation into osteoblasts and mediates osteogenic differentiation induced by dexamethasone in MSCs through activation of Wnt/beta-catenin signaling- dependent Runx2 expression. |
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Authors:
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Zahia Hamidouche; Eric Haÿ; Pascal Vaudin; Pierre Charbord; Roland Schüle; Pierre J Marie; Olivia Fromigué |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2008-07-24 |
Journal Detail:
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Title: FASEB journal : official publication of the Federation of American Societies for Experimental Biology Volume: 22 ISSN: 1530-6860 ISO Abbreviation: FASEB J. Publication Date: 2008 Nov |
Date Detail:
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Created Date: 2008-10-31 Completed Date: 2008-11-18 Revised Date: 2012-02-15 |
Medline Journal Info:
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Nlm Unique ID: 8804484 Medline TA: FASEB J Country: United States |
Other Details:
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Languages: eng Pagination: 3813-22 Citation Subset: IM |
Affiliation:
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INSERM U606, Hopital Lariboisiere, 2 rue Ambroise Pare, 75475 Paris cedex 10, France. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Active Transport, Cell Nucleus
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drug effects,
physiology Alkaline Phosphatase Animals Anti-Inflammatory Agents / pharmacology* Calcification, Physiologic / drug effects, physiology Cell Differentiation / drug effects*, physiology Cell Line Cell Nucleus / genetics, metabolism* Cells, Cultured Collagen Type I / genetics, metabolism Core Binding Factor Alpha 1 Subunit / biosynthesis*, genetics Dexamethasone / pharmacology* Enzyme Activators / metabolism Extracellular Matrix / genetics, metabolism Homeodomain Proteins / genetics, metabolism* Humans Intercellular Signaling Peptides and Proteins / genetics, metabolism LIM-Homeodomain Proteins Mesenchymal Stem Cells / cytology, metabolism* Mice Muscle Proteins / genetics, metabolism* Mutation Osteogenesis / drug effects, physiology Signal Transduction / drug effects*, physiology TCF Transcription Factors / genetics, metabolism Transcription Factors / genetics, metabolism* Up-Regulation / drug effects, physiology* Wnt Proteins / genetics, metabolism* beta Catenin / genetics, metabolism* |
| Chemical | |
Reg. No./Substance:
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0/Anti-Inflammatory Agents; 0/CTNNB1 protein, human; 0/Catnb protein, mouse; 0/Collagen Type I; 0/Core Binding Factor Alpha 1 Subunit; 0/DKK1 protein, human; 0/Dkk1 protein, mouse; 0/Enzyme Activators; 0/FHL2 protein, human; 0/Fhl2 protein, mouse; 0/Homeodomain Proteins; 0/Intercellular Signaling Peptides and Proteins; 0/LIM-Homeodomain Proteins; 0/Muscle Proteins; 0/RUNX2 protein, human; 0/Runx2 protein, mouse; 0/TCF Transcription Factors; 0/Transcription Factors; 0/Wnt Proteins; 0/beta Catenin; 50-02-2/Dexamethasone; EC 3.1.3.1/Alkaline Phosphatase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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