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Calcified Tissue International
Published in: Calcified Tissue International 6/2010

01-12-2010

Integration of Phosphatidylinositol 3-Kinase, Akt Kinase, and Smad Signaling Pathway in BMP-2-Induced Osterix Expression

Authors: Chandi Charan Mandal, Hicham Drissi, Goutam Ghosh Choudhury, Nandini Ghosh-Choudhury

Published in: Calcified Tissue International | Issue 6/2010

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Abstract

Osterix (Osx), a BMP-2-regulated transcription factor, controls expression of genes essential for osteoblast differentiation. Using progressive deletion of the Osx promoter, we characterized a Smad binding element (SBE) between −552 and −839 bp from its transcription start site. Electrophoretic mobility shift assay and chromatin immunoprecipitation assay showed binding and in vivo recruitment of Smads 1 and 5 to the Osx SBE. Inactivation of PI 3-kinase by the pharmacologic inhibitor Ly294002 or by dominant negative (DN) enzyme significantly blocked BMP-2-induced Osx protein and mRNA expression and Osx transcription. Finally, both DN PI 3-kinase and DN Akt significantly attenuated Smad 5-dependent transcription of Osx, demonstrating the first evidence for a concerted action of PI 3-kinase/Akt signaling with BMP-specific Smads for expression of Osx.
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Metadata
Title
Integration of Phosphatidylinositol 3-Kinase, Akt Kinase, and Smad Signaling Pathway in BMP-2-Induced Osterix Expression
Authors
Chandi Charan Mandal
Hicham Drissi
Goutam Ghosh Choudhury
Nandini Ghosh-Choudhury
Publication date
01-12-2010
Publisher
Springer-Verlag
Published in
Calcified Tissue International / Issue 6/2010
Print ISSN: 0171-967X
Electronic ISSN: 1432-0827
DOI
https://doi.org/10.1007/s00223-010-9419-3

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