The IRE1alpha-XBP1 pathway is essential for osteoblast differentiation through promoting transcription of Osterix
Program in Gene Function and Expression; Program in Molecular Medicine
Medical Subject Headings
Unfolded Protein Response; Osteoblasts; Cell Differentiation; Transcription Factors; Endoribonucleases; Protein-Serine-Threonine Kinases; DNA-Binding Proteins
Genetics and Genomics
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 1alpha (IRE1alpha), 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 IRE1alpha-XBP1 pathway is involved in osteoblast differentiation through promoting Osx transcription.
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Citation: EMBO Rep. 2011 May 1;12(5):451-7. Epub 2011 Mar 18. Link to article on publisher's site