Integration of phosphatidylinositol 3-kinase, akt kinase, and smad signaling pathway in BMP-2-induced osterix expression

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

Research output: Contribution to journalArticlepeer-review

27 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)533-540
Number of pages8
JournalCalcified tissue international
Volume87
Issue number6
DOIs
StatePublished - Dec 2010

Keywords

  • Bone morphogenetic protein
  • Gene transcription regulation
  • Osteoblast
  • Osterix
  • PI 3-kinase
  • Smad

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Orthopedics and Sports Medicine
  • Endocrinology

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