The IRE1α-XBP1 pathway is essential for osteoblast differentiation through promoting transcription of Osterix

Takahide Tohmonda, Yoshiteru Miyauchi, Rajarshi Ghosh, Masaki Yoda, Shinichi Uchikawa, Jiro Takito, Hideo Morioka, Masaya Nakamura, Takao Iwawaki, Kazuhiro Chiba, Yoshiaki Toyama, Fumihiko Urano, Keisuke Horiuchi

Research output: Contribution to journalArticle

68 Citations (Scopus)

Abstract

During skeletal development, osteoblasts produce large amounts of extracellular matrix proteins and must therefore increase their secretory machinery to handle the deposition. The accumulation of unfolded protein in the endoplasmic reticulum induces an adoptive mechanism called the unfolded protein response (UPR). We show that one of the most crucial UPR mediators, inositol-requiring protein 1α (IRE1α), and its target transcription factor X-box binding protein 1 (XBP1), are essential for bone morphogenic protein 2-induced osteoblast differentiation. Furthermore, we identify Osterix (Osx, a transcription factor that is indispensible for bone formation) as a target gene of XBP1. The promoter region of the Osx gene encodes two potential binding motifs for XBP1, and we show that XBP1 binds to these regions. Thus, the IRE1α-XBP1 pathway is involved in osteoblast differentiation through promoting Osx transcription.

Original languageEnglish
Pages (from-to)451-457
Number of pages7
JournalEMBO Reports
Volume12
Issue number5
DOIs
Publication statusPublished - 2011 May 1

Keywords

  • IRE1α
  • Osterix
  • XBP1
  • osteoblast differentiation
  • unfolded protein response

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Genetics

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  • Cite this

    Tohmonda, T., Miyauchi, Y., Ghosh, R., Yoda, M., Uchikawa, S., Takito, J., Morioka, H., Nakamura, M., Iwawaki, T., Chiba, K., Toyama, Y., Urano, F., & Horiuchi, K. (2011). The IRE1α-XBP1 pathway is essential for osteoblast differentiation through promoting transcription of Osterix. EMBO Reports, 12(5), 451-457. https://doi.org/10.1038/embor.2011.34