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Mitogen Activated Protein Kinase-Dependent Inhibition of Osteocalcin Gene Expression by Transforming Growth Factor-β1

Publication Type : Journal Article

Thematic Areas : Nanosciences and Molecular Medicine

Publisher : Journal of Cellular Biochemistry

Source : Journal of Cellular Biochemistry, Volume 106, Number 1, p.161-169 (2009)

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Keywords : alkaline phosphatase, animal cell, Animals, article, bone development, cell differentiation, collagen type 1, controlled study, Core Binding Factor Alpha 1 Subunit, enzyme inhibition, gene expression, Humans, mitogen activated protein kinase, mitogen activated protein kinase inhibitor, Mitogen-Activated Protein Kinases, nonhuman, osteoblast, Osteoblasts, osteocalcin, Phosphorylation, priority journal, protein DNA binding, protein function, protein localization, protein phosphorylation, protein processing, protein protein interaction, rat, Rats, transcription factor RUNX2, Transfection, transforming growth factor beta1

Campus : Kochi

School : Center for Nanosciences

Center : Amrita Center for Nanosciences and Molecular Medicine Move, Nanosciences

Department : Nanosciences

Year : 2009

Abstract : TGF-β (transforming growth factor-beta) plays a key role in osteoblast differentiation and bone development. While the ability of TGF-β to inhibit the expression of osteoblast differentiation genes has been well documented, the mechanism of this inhibition is not yet completely characterized. Runx2, a transcription factor necessary for expression of osteoblast differentiation genes is a central target of inhibition by TGF-β. In this study, we found that TGF-β1 inhibits expression of osteoblast differentiation genes without altering expression of Runx2. Transient transfection experiments determined that TGF-β1 inhibited osteocalcin promoter activity and this effect is mediated through Runx2. We further identified that there was no change in protein expression, cellular localization, or DNA binding affinity of Runx2 after TGF-β1-treatment of osteoblasts, suggesting that Runx2 undergoes post-translational modifications following TGF-β1 treatment. Coimmunoprecipitation experiments identified increased phosphorylation of Runx2 when differentiating osteoblasts were treated with TGF-β1. Mitogen activated protein kinase (MAPK) inhibitors relieved the TGF-β1-inhibitory effect of Runx2-mediated osteocalcin expression. Thus, our results suggest that TGF-β1-inhibition of osteoblast differentiation is dependent on the MAPK pathway and this effect is most likely mediated by post-translational modification of Runx2 such as phosphorylation rather than other regulatory mechanisms. J. Cell. Biochem. 106: 161-169, 2009. copy; 2008 Wiley-Liss, Inc.

Cite this Research Publication : S. Kwok, Partridge, N. C., Srinivasan, N., Shantikumar V Nair, and Selvamurugan, N., “Mitogen Activated Protein Kinase-Dependent Inhibition of Osteocalcin Gene Expression by Transforming Growth Factor-β1”, Journal of Cellular Biochemistry, vol. 106, pp. 161-169, 2009.

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