Src enhances osteogenic differentiation through phosphorylation of Osterix

Mol Cell Endocrinol. 2015 May 15:407:85-97. doi: 10.1016/j.mce.2015.03.010. Epub 2015 Mar 20.

Abstract

Osterix, a zinc-finger transcription factor, is required for osteoblast differentiation and new bone formation during embryonic development. The c-Src of tyrosine kinase is involved in a variety of cellular signaling pathways, leading to the induction of DNA synthesis, cell proliferation, and cytoskeletal reorganization. Src activity is tightly regulated and its dysregulation leads to constitutive activation and cellular transformation. The function of Osterix can be also modulated by post-translational modification. But the precise molecular signaling mechanisms between Osterix and c-Src are not known. In this study we investigated the potential regulation of Osterix function by c-Src in osteoblast differentiation. We found that c-Src activation increases protein stability, osteogenic activity and transcriptional activity of Osterix. The siRNA-mediated knockdown of c-Src decreased the protein levels and transcriptional activity of Osterix. Conversely, Src specific inhibitor, SU6656, decreased the protein levels and transcriptional activity of Osterix. The c-Src interacts with and phosphorylates Osterix. These results suggest that c-Src signaling modulates osteoblast differentiation at least in part through Osterix.

Keywords: Differentiation; Osteoblast; Osterix; Phosphorylation; Src.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CSK Tyrosine-Protein Kinase
  • Cell Differentiation
  • Cell Line
  • Cell Proliferation
  • Cytoskeleton / metabolism
  • Cytoskeleton / ultrastructure
  • DNA / biosynthesis
  • DNA / genetics
  • Epithelial Cells / cytology
  • Epithelial Cells / drug effects
  • Epithelial Cells / metabolism*
  • Gene Expression Regulation
  • Genes, Reporter
  • HEK293 Cells
  • Humans
  • Indoles / pharmacology
  • Luciferases / genetics
  • Luciferases / metabolism
  • Mice
  • Myoblasts / cytology
  • Myoblasts / drug effects
  • Myoblasts / metabolism*
  • Osteoblasts / cytology
  • Osteoblasts / drug effects
  • Osteoblasts / metabolism*
  • Osteogenesis / genetics
  • Protein Kinase Inhibitors / pharmacology
  • Protein Stability
  • RNA, Small Interfering / genetics
  • RNA, Small Interfering / metabolism
  • Signal Transduction
  • Sp7 Transcription Factor
  • Sulfonamides / pharmacology
  • Transcription Factors / genetics*
  • Transcription Factors / metabolism
  • src-Family Kinases / antagonists & inhibitors
  • src-Family Kinases / genetics*
  • src-Family Kinases / metabolism

Substances

  • Indoles
  • Protein Kinase Inhibitors
  • RNA, Small Interfering
  • SU 6656
  • Sp7 Transcription Factor
  • SP7 protein, human
  • Sulfonamides
  • Transcription Factors
  • DNA
  • Luciferases
  • CSK Tyrosine-Protein Kinase
  • src-Family Kinases
  • CSK protein, human