TGF-β prevents the denervation-induced reduction of bone formation and promotes the bone regeneration through inhibiting ubiquitin-proteasome pathway

Biosci Rep. 2019 May 14;39(5):BSR20190350. doi: 10.1042/BSR20190350. Print 2019 May 31.

Abstract

Background: Transforming growth factor beta (TGF-β) can stimulate osteogenesis as a multifunctional protein. The present study was to explore if TGF-β can prevent denervation-induced reduction of bone formation.Materials & methods: The 6-week-old male mice were treated with recombinant human TGF-β1 (rhTGF-β1). Bone formation, endochondral bone growth rates, and gene expression of osteoblast markers were measured in the skeletal tissue by real-time PCR.Results: RhTGF-β1 treatment prevented the denervation-induced decrease in bone formation rates, endochondral growth, and expression of Cbfa1/Runx2 (runt-related transcription factor 2), Ostecalcin (OC), and ColIA1. TGF-β1 partially inhibited the denervation-induced ubiquitination of Cbfa1/Runx2 in mouse cancellous bones via ubiquitin-proteasome pathway.Conclusion: TGF-β prevents denervation-induced reduction of bone formation and promotes the bone regeneration through inhibiting ubiquitin-proteasome pathway at least partially.

Keywords: Bone Formation; Dernervation; RUNX2; TGF-β; regeneration; ubiquitins.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone Regeneration / drug effects*
  • Humans
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Osteogenesis / drug effects*
  • Proteasome Endopeptidase Complex / metabolism*
  • Recombinant Proteins / pharmacology
  • Signal Transduction / drug effects
  • Transforming Growth Factor beta / pharmacology*
  • Ubiquitin / metabolism*

Substances

  • Recombinant Proteins
  • Transforming Growth Factor beta
  • Ubiquitin
  • Proteasome Endopeptidase Complex