Src enhances osteogenic differentiation through phosphorylation of Osterix

You Hee Choi, Youn Ho Han, Sung Ho Lee, Heesun Cheong, Kwang Hoon Chun, Chang Yeol Yeo, Kwang Youl Lee

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

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.

Original languageEnglish
Pages (from-to)85-97
Number of pages13
JournalMolecular and Cellular Endocrinology
Volume407
DOIs
StatePublished - 5 May 2015

Keywords

  • Differentiation
  • Osteoblast
  • Osterix
  • Phosphorylation
  • Src

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