title: The unfolded protein response in skeletal development and homeostasis.
abstract: 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.
authors.affiliation: Department of Orthopedic Surgery, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan. horiuchi@z3.keio.jp.|Department of Anti-aging Orthopedic Research, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan. horiuchi@z3.keio.jp.
authors.forename: Keisuke
authors.identifier: 0000-0001-7063-9609
authors.initials: K
authors.lastname: Horiuchi
authors.affiliation: Department of Orthopedic Surgery, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan.|Department of Anti-aging Orthopedic Research, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan.
authors.forename: Takahide
authors.initials: T
authors.lastname: Tohmonda
authors.affiliation: Department of Orthopedic Surgery, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan.
authors.forename: Hideo
authors.initials: H
authors.lastname: Morioka
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D019902:Chondrocytes / Q000166:cytology* / Q000378:metabolism; D020219:Chondrogenesis; D006706:Homeostasis; D006801:Humans; D010006:Osteoblasts / Q000166:cytology* / Q000378:metabolism; D010010:Osteoclasts / Q000166:cytology* / Q000378:metabolism; D010012:Osteogenesis; D015398:Signal Transduction; D056811:Unfolded Protein Response
keywords: ATF6; Chondrocyte; ER stress; IRE1α; Osteoblast; Osteoclast; PERK; Unfolded protein response