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Myocyte enhancer factor 2C : an osteoblast transcription factor identified by DMSO enhanced mineralization

Stephens, Alexandre S., Stephens, Sebastian R., Hobbs, Carl, Hutmacher, Dietmar W., Bacic-Welsh, Desa, Woodruff, Maria A., & Morrison, Nigel A. (2011) Myocyte enhancer factor 2C : an osteoblast transcription factor identified by DMSO enhanced mineralization. Journal of Biological Chemistry.

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Abstract

Rapid mineralization of cultured osteoblasts could be a useful characteristic in stem-cell mediated therapies for fracture and other orthopaedic problems. Dimethyl sulfoxide (DMSO) is a small amphipathic solvent molecule capable of simulating cell differentiation. We report that, in primary human osteoblasts, DMSO dose-dependently enhanced the expression of osteoblast differentiation markers alkaline phosphatase (ALP) activity and extracellular matrix mineralization. Furthermore, similar DMSO mediated mineralization enhancement was observed in primary osteoblast-like cells differentiated from mouse mesenchymal cells derived from fat, a promising source of starter cells for cell-based therapy. Using a convenient mouse pre-osteoblast model cell line MC3T3-E1 we further investigated this phenomenon showing that numerous osteoblast-expressed genes were elevated in response to DMSO treatment and correlated with enhanced mineralization. Myocyte enhancer factor 2c (Mef2c) was identified as the transcription factor most induced by DMSO, among numerous DMSO-induced genes, suggesting a role for Mef2c in osteoblast gene regulation. Immunohistochemistry confirmed expression of Mef2c in osteoblast-like cells in mouse mandible, cortical and trabecular bone. shRNAi-mediated Mef2c gene silencing resulted in defective osteoblast differentiation, decreased ALP activity and matrix mineralization and knockdown of osteoblast specific gene expression, including osteocalcin and bone sialoprotein. Flow on knockdown of bone specific transcription factors, Runx2 and osterix by shRNAi knockdown of Mef2c suggests that Mef2c lies upstream of these two important factors in the cascade of gene expression in osteoblasts.

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7 citations in Scopus
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4 citations in Web of Science®

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ID Code: 43386
Item Type: Journal Article
Additional Information: First Published on June 7, 2011
Keywords: Bone, Cell differentiation, Matrix metalloproteinase (MMP), siRNA, Transcription factors, DMSO, MEF2c, mineralization, osteoblast, osteocalcin
DOI: 10.1074/jbc.M111.253518
ISSN: 0021-9258
Subjects: Australian and New Zealand Standard Research Classification > ENGINEERING (090000) > BIOMEDICAL ENGINEERING (090300) > Biomaterials (090301)
Divisions: Past > QUT Faculties & Divisions > Faculty of Built Environment and Engineering
Current > Institutes > Institute of Health and Biomedical Innovation
Copyright Owner: Copyright 2011 American Society for Biochemistry and Molecular Biology
Deposited On: 20 Jul 2011 10:33
Last Modified: 07 Aug 2012 18:05

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