BMP-2-induced Osterix Expression Is Mediated by Dlx5 but Is Independent of Runx2

Biochem Biophys Res Commun. 2003 Sep 26;309(3):689-94. doi: 10.1016/j.bbrc.2003.08.058.

Abstract

BMP-2 stimulates the expression of three osteogenic master transcription factors: Runx2, Dlx5, and Osterix (Osx). However, the hierarchical regulatory relationships among them are not yet clearly understood. Osx was commonly stimulated in osteogenic and non-osteogenic cells in response to BMP-signaling, as Dlx5 was in our previous report. A cycloheximide experiment indicated that Osx expression by BMP-2 requires new protein synthesis. Even if Osx has been suggested as a downstream target of Runx2, the results of this study indicated that Osx expression was still induced by BMP-2 treatment in Runx2 null cells, but not induced by Runx2 overexpression in myogenic C2C12 cells. Instead, Osx expression by BMP-2 was completely abrogated by the antisense blocking of Dlx5. Depending upon the coincident expression pattern of Osx and Dlx5, and the blocking of Osx expression by the antisense Dlx5, BMP-2-induced Osx expression is mainly mediated not by Runx2, but by Dlx5.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone Morphogenetic Protein 2
  • Bone Morphogenetic Proteins / pharmacology*
  • Cell Differentiation
  • Cell Line
  • Core Binding Factor Alpha 1 Subunit
  • Gene Expression Regulation
  • Homeodomain Proteins / physiology*
  • Mice
  • Models, Biological
  • Neoplasm Proteins*
  • Osteoblasts / cytology
  • Osteoblasts / drug effects
  • Osteoblasts / metabolism*
  • Rats
  • Sp7 Transcription Factor
  • Transcription Factors / biosynthesis*
  • Transcription Factors / genetics
  • Transcription Factors / physiology*
  • Transforming Growth Factor beta*

Substances

  • Bmp2 protein, mouse
  • Bmp2 protein, rat
  • Bone Morphogenetic Protein 2
  • Bone Morphogenetic Proteins
  • Core Binding Factor Alpha 1 Subunit
  • Dlx5 protein, mouse
  • Homeodomain Proteins
  • Neoplasm Proteins
  • Sp7 Transcription Factor
  • Sp7 protein, human
  • Transcription Factors
  • Transforming Growth Factor beta