eIF2α signaling regulates ischemic osteonecrosis through endoplasmic reticulum stress

Abstract Osteonecrosis of the femoral head (ONFH) primarily results from ischemia/hypoxia to the femoral head, and one of the cellular manifestations is the endoplasmic reticulum (ER) stress. To understand possible linkage of ischemic osteonecrosis to the ER stress, a surgery-induced animal model wa...

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Autores principales:	Daquan Liu, Yunlong Zhang, Xinle Li, Jie Li, Shuang Yang, Xiaoxue Xing, Guanwei Fan, Hiroki Yokota, Ping Zhang
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/8eec0e8f41b8472a8778f0f1919533e3
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spelling	oai:doaj.org-article:8eec0e8f41b8472a8778f0f1919533e32021-12-02T16:06:56ZeIF2α signaling regulates ischemic osteonecrosis through endoplasmic reticulum stress10.1038/s41598-017-05488-62045-2322https://doaj.org/article/8eec0e8f41b8472a8778f0f1919533e32017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-05488-6https://doaj.org/toc/2045-2322Abstract Osteonecrosis of the femoral head (ONFH) primarily results from ischemia/hypoxia to the femoral head, and one of the cellular manifestations is the endoplasmic reticulum (ER) stress. To understand possible linkage of ischemic osteonecrosis to the ER stress, a surgery-induced animal model was employed and salubrinal was administered to evaluate the role of ER stress. Salubrinal is a synthetic chemical that inhibits de-phosphorylation of eIF2α, and it can suppress cell death from the ER stress at a proper dose. The results indicated that the ER stress was associated with ONFH and salubrinal significantly improved ONFH-induced symptoms such as osteonecrosis, bone loss, reduction in vessel perfusion, and excessive osteoclastogenesis in the femoral head. Salubrinal also protected osteoblast development by upregulating the levels of ATF4, ALP and RUNX2, and it stimulated angiogenesis of endothelial cells through elevating ATF4 and VEGF. Collectively, the results support the notion that the ER stress is an important pathological outcome in the surgery-induced ONFH model, and salubrinal improves ONFH symptoms by enhancing angiogenesis and bone healing via suppressing the ER stress.Daquan LiuYunlong ZhangXinle LiJie LiShuang YangXiaoxue XingGuanwei FanHiroki YokotaPing ZhangNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-14 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Daquan Liu Yunlong Zhang Xinle Li Jie Li Shuang Yang Xiaoxue Xing Guanwei Fan Hiroki Yokota Ping Zhang eIF2α signaling regulates ischemic osteonecrosis through endoplasmic reticulum stress
description	Abstract Osteonecrosis of the femoral head (ONFH) primarily results from ischemia/hypoxia to the femoral head, and one of the cellular manifestations is the endoplasmic reticulum (ER) stress. To understand possible linkage of ischemic osteonecrosis to the ER stress, a surgery-induced animal model was employed and salubrinal was administered to evaluate the role of ER stress. Salubrinal is a synthetic chemical that inhibits de-phosphorylation of eIF2α, and it can suppress cell death from the ER stress at a proper dose. The results indicated that the ER stress was associated with ONFH and salubrinal significantly improved ONFH-induced symptoms such as osteonecrosis, bone loss, reduction in vessel perfusion, and excessive osteoclastogenesis in the femoral head. Salubrinal also protected osteoblast development by upregulating the levels of ATF4, ALP and RUNX2, and it stimulated angiogenesis of endothelial cells through elevating ATF4 and VEGF. Collectively, the results support the notion that the ER stress is an important pathological outcome in the surgery-induced ONFH model, and salubrinal improves ONFH symptoms by enhancing angiogenesis and bone healing via suppressing the ER stress.
format	article
author	Daquan Liu Yunlong Zhang Xinle Li Jie Li Shuang Yang Xiaoxue Xing Guanwei Fan Hiroki Yokota Ping Zhang
author_facet	Daquan Liu Yunlong Zhang Xinle Li Jie Li Shuang Yang Xiaoxue Xing Guanwei Fan Hiroki Yokota Ping Zhang
author_sort	Daquan Liu
title	eIF2α signaling regulates ischemic osteonecrosis through endoplasmic reticulum stress
title_short	eIF2α signaling regulates ischemic osteonecrosis through endoplasmic reticulum stress
title_full	eIF2α signaling regulates ischemic osteonecrosis through endoplasmic reticulum stress
title_fullStr	eIF2α signaling regulates ischemic osteonecrosis through endoplasmic reticulum stress
title_full_unstemmed	eIF2α signaling regulates ischemic osteonecrosis through endoplasmic reticulum stress
title_sort	eif2α signaling regulates ischemic osteonecrosis through endoplasmic reticulum stress
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/8eec0e8f41b8472a8778f0f1919533e3
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_version_	1718384789731409920

eIF2α signaling regulates ischemic osteonecrosis through endoplasmic reticulum stress

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