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

doi:10.1038/embor.2011.34

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

Department of Orthopaedics

Research output: Contribution to journal › Article › peer-review

97 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 language	English
Pages (from-to)	451-457
Number of pages	7
Journal	EMBO Reports
Volume	12
Issue number	5
DOIs	https://doi.org/10.1038/embor.2011.34
Publication status	Published - 2011 May 1

Keywords

IRE1α
Osterix
XBP1
osteoblast differentiation
unfolded protein response

ASJC Scopus subject areas

Biochemistry
Molecular Biology
Genetics

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10.1038/embor.2011.34

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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.",

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AU - Yoda, Masaki

AU - Uchikawa, Shinichi

AU - Takito, Jiro

AU - Morioka, Hideo

AU - Nakamura, Masaya

AU - Iwawaki, Takao

AU - Chiba, Kazuhiro

AU - Toyama, Yoshiaki

AU - Urano, Fumihiko

AU - Horiuchi, Keisuke

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N2 - 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.

AB - 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.

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

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Keywords

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