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

研究成果: Article査読

88 被引用数 (Scopus)

抄録

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.

本文言語English
ページ(範囲)451-457
ページ数7
ジャーナルEMBO Reports
12
5
DOI
出版ステータスPublished - 2011 5月 1

ASJC Scopus subject areas

  • 生化学
  • 分子生物学
  • 遺伝学

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