title: Roles of the endoplasmic reticulum stress transducer OASIS in fracture healing.
abstract: A new type of endoplasmic reticulum (ER) stress transducer, Old Astrocyte Specifically Induced Substance (OASIS), which is induced by bone morphogenetic protein-2 (BMP2), has been reported to activate the transcription of type I collagen and contribute to the secretion of bone matrix proteins in osteoblasts. Here, we examined the role of OASIS in fracture healing using the fracture models in wild-type (WT) and OASIS(-/-) mice. We found that the expression of OASIS mRNA was induced after fracture. Micro-computed tomography indicated that the callus density of OASIS(-/-) mice was less than that of WT mice, and the newly formed bone in OASIS(-/-) mice exhibited a decrease of the bone volume by bone morphometric analysis. Biomechanically, the callus bone strength of OASIS(-/-) mice was inferior to that of WT mice. Based on RT-PCR, in situ hybridization, immunohistochemical, and electrophoretic analyses, it was clarified that the synthesis of type I collagen was impaired in OASIS(-/-) mice. Electron microscopic analysis revealed that OASIS(-/-) osteoblasts in the fracture callus contained the abnormal expansion of the ERs, similar to OASIS(-/-) osteoblasts in the normal skeletal development. Thus, OASIS may play a role in bone formation through the expression of type I collagen and the secretion of bone matrix proteins in fracture healing.
authors.affiliation: Division of Orthopedic Surgery, Department of Medicine of Sensory and Motor Organs, Faculty of Medicine, University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki 889-1692, Japan.
authors.forename: Taro
authors.initials: T
authors.lastname: Funamoto
authors.forename: Tomohisa
authors.initials: T
authors.lastname: Sekimoto
authors.forename: Tomohiko
authors.initials: T
authors.lastname: Murakami
authors.forename: Syuji
authors.initials: S
authors.lastname: Kurogi
authors.forename: Kazunori
authors.initials: K
authors.lastname: Imaizumi
authors.forename: Etsuo
authors.initials: E
authors.lastname: Chosa
mesh_terms: D000818:Animals; D002146:Bony Callus / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D024042:Collagen Type I / Q000235:genetics / Q000378:metabolism; D017362:Cyclic AMP Response Element-Binding Protein / Q000172:deficiency / Q000378:metabolism*; D004195:Disease Models, Animal; D004721:Endoplasmic Reticulum / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D059865:Endoplasmic Reticulum Stress / Q000235:genetics; D005264:Femoral Fractures / Q000000981:diagnostic imaging / Q000473:pathology; D017102:Fracture Healing / Q000235:genetics; D005786:Gene Expression Regulation; D051379:Mice; D009419:Nerve Tissue Proteins / Q000172:deficiency / Q000378:metabolism*; D010006:Osteoblasts / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D055114:X-Ray Microtomography
chemical_list: D024042:Collagen Type I; C119923:Creb3l1 protein, mouse; D017362:Cyclic AMP Response Element-Binding Protein; D009419:Nerve Tissue Proteins