Peptide drugs accelerate BMP-2-induced calvarial bone regeneration and stimulate osteoblast differentiation through mTORC1 signaling

Yasutaka Sugamori, Setsuko Mise-Omata, Chizuko Maeda, Shigeki Aoki, Yasuhiko Tabata, Ramachandran Murali, Hisataka Yasuda, Nobuyuki Udagawa, Hiroshi Suzuki, Masashi Honma, Kazuhiro Aoki

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Both W9 and OP3-4 were known to bind the receptor activator of NF-κB ligand (RANKL), inhibiting osteoclastogenesis. Recently, both peptides were shown to stimulate osteoblast differentiation; however, the mechanism underlying the activity of these peptides remains to be clarified. A primary osteoblast culture showed that rapamycin, an mTORC1 inhibitor, which was recently demonstrated to be an important serine/threonine kinase for bone formation, inhibited the peptide-induced alkaline phosphatase activity. Furthermore, both peptides promoted the phosphorylation of Akt and S6K1, an upstream molecule of mTORC1 and the effector molecule of mTORC1, respectively. In the in vivo calvarial defect model, W9 and OP3-4 accelerated BMP-2-induced bone formation to a similar extent, which was confirmed by histomorphometric analyses using fluorescence images of undecalcified sections. Our data suggest that these RANKL-binding peptides could stimulate the mTORC1 activity, which might play a role in the acceleration of BMP-2-induced bone regeneration by the RANKL-binding peptides.

Original languageEnglish
Pages (from-to)717-725
Number of pages9
JournalBioEssays
Volume38
Issue number8
DOIs
Publication statusPublished - 2016 Aug 1
Externally publishedYes

Keywords

  • BMP-2
  • bone regeneration
  • histomorphometry
  • mTORC1
  • osteoblast differentiation
  • peptide therapeutics
  • rapamycin

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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  • Cite this

    Sugamori, Y., Mise-Omata, S., Maeda, C., Aoki, S., Tabata, Y., Murali, R., Yasuda, H., Udagawa, N., Suzuki, H., Honma, M., & Aoki, K. (2016). Peptide drugs accelerate BMP-2-induced calvarial bone regeneration and stimulate osteoblast differentiation through mTORC1 signaling. BioEssays, 38(8), 717-725. https://doi.org/10.1002/bies.201600104