Bone morphogenetic protein 9 (BMP9) directly induces Notch effector molecule Hes1 through the SMAD signaling pathway in osteoblasts

Chang Hwan Seong, Norika Chiba, Joji Kusuyama, Muhammad Subhan Amir, Nahoko Eiraku, Sachiko Yamashita, Tomokazu Ohnishi, Norifumi Nakamura, Tetsuya Matsuguchi

Research output: Contribution to journalArticlepeer-review

Abstract

Bone morphogenetic protein (BMP) 9 is one of the most osteogenic BMPs, but its mechanism of action has not been fully elucidated. Hes1, a transcriptional regulator with a basic helix-loop-helix domain, is a well-known effector of Notch signaling. Here, we find that BMP9 induces periodic increases of Hes1 mRNA and protein expression in osteoblasts, presumably through an autocrine negative feedback mechanism. BMP9-mediated Hes1 induction is significantly inhibited by an ALK inhibitor and overexpression of Smad7, an inhibitory Smad. Luciferase and ChIP assays revealed that two Smad-binding sites in the 5′ upstream region of the mouse Hes1 gene are essential for transcriptional activation by BMP9. Thus, our data indicate that BMP9 induces Hes1 expression in osteoblasts via the Smad signaling pathway.

Original languageEnglish
Pages (from-to)389-403
Number of pages15
JournalFEBS Letters
Volume595
Issue number3
DOIs
Publication statusPublished - 2021 Feb

Keywords

  • Bone Morphogenetic Protein 9
  • Hes1
  • bone regeneration
  • notch
  • osteogenic differentiation

ASJC Scopus subject areas

  • Biophysics
  • Structural Biology
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Cell Biology

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