Journal
CALCIFIED TISSUE INTERNATIONAL
Volume 87, Issue 6, Pages 533-540Publisher
SPRINGER
DOI: 10.1007/s00223-010-9419-3
Keywords
Bone morphogenetic protein; Osterix; PI 3-kinase; Smad; Gene transcription regulation; Osteoblast
Categories
Funding
- NIH [RO1 AR52425, RO1 DK50190]
- VA Medical Research Service Merit Review
- VA Merit Review
- Juvenile Diabetes Research Foundation
- Department of Veterans Affairs
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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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