The unfolded protein response in skeletal development and homeostasis

Keisuke Horiuchi, Takahide Tohmonda, Hideo Morioka

Research output: Contribution to journalReview articlepeer-review

38 Citations (Scopus)


Osteoblasts and chondrocytes produce a large number of extracellular matrix proteins to generate and maintain the skeletal system. To cope with their functions as secretory cells, these cells must acquire a considerable capacity for protein synthesis and also the machinery for the quality-control and transport of newly synthesized secreted proteins. The unfolded protein response (UPR) plays a crucial role during the differentiation of these cells to achieve this goal. Unexpectedly, however, studies in the past several years have revealed that the UPR has more extensive functions in skeletal development than was initially assumed, and the UPR critically orchestrates many facets of skeletal development and homeostasis. This review focuses on recent findings on the functions of the UPR in the differentiation of osteoblasts, chondrocytes, and osteoclasts. These findings may have a substantial impact on our understanding of bone metabolism and also on establishing treatments for congenital and acquired skeletal disorders.

Original languageEnglish
Pages (from-to)2851-2869
Number of pages19
JournalCellular and Molecular Life Sciences
Issue number15
Publication statusPublished - 2016 Aug 1


  • ATF6
  • Chondrocyte
  • ER stress
  • IRE1α
  • Osteoblast
  • Osteoclast
  • PERK
  • Unfolded protein response

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Pharmacology
  • Cellular and Molecular Neuroscience
  • Cell Biology


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