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Roles of the endoplasmic reticulum stress transducer OASIS in fracture healing

Authors :
Syuji Kurogi
Taro Funamoto
Tomohiko Murakami
Kazunori Imaizumi
Etsuo Chosa
Tomohisa Sekimoto
Source :
Bone. 49:724-732
Publication Year :
2011
Publisher :
Elsevier BV, 2011.

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.

Details

ISSN :
87563282
Volume :
49
Database :
OpenAIRE
Journal :
Bone
Accession number :
edsair.doi.dedup.....622abcf75b458ed3edbcb1f495bbed4c
Full Text :
https://doi.org/10.1016/j.bone.2011.06.012