Chronic Ethanol Consumption Induces Osteopenia via Activation of Osteoblast Necroptosis

Chronic high-dose alcohol consumption impairs bone remodeling, reduces bone mass, and increases the risk of osteoporosis and bone fracture. However, the mechanisms underlying alcohol-induced osteoporosis are yet to be elucidated. In this study, we showed that excess intake of ethyl alcohol (EtOH) re...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Man Guo, Yong-Li Huang, Qi Wu, Li Chai, Zong-Zhe Jiang, Yan Zeng, Sheng-Rong Wan, Xiao-Zhen Tan, Yang Long, Jun-Ling Gu, Fang-Yuan Teng, Yong Xu
Formato:	article
Lenguaje:	EN
Publicado:	Hindawi Limited 2021
Materias:	Cytology QH573-671
Acceso en línea:	https://doaj.org/article/f3b28d7747414e8bbe64aa2e9305badb
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:f3b28d7747414e8bbe64aa2e9305badb
record_format	dspace
spelling	oai:doaj.org-article:f3b28d7747414e8bbe64aa2e9305badb2021-11-08T02:35:22ZChronic Ethanol Consumption Induces Osteopenia via Activation of Osteoblast Necroptosis1942-099410.1155/2021/3027954https://doaj.org/article/f3b28d7747414e8bbe64aa2e9305badb2021-01-01T00:00:00Zhttp://dx.doi.org/10.1155/2021/3027954https://doaj.org/toc/1942-0994Chronic high-dose alcohol consumption impairs bone remodeling, reduces bone mass, and increases the risk of osteoporosis and bone fracture. However, the mechanisms underlying alcohol-induced osteoporosis are yet to be elucidated. In this study, we showed that excess intake of ethyl alcohol (EtOH) resulted in osteopenia and osteoblast necroptosis in mice that led to necrotic lesions and reduced osteogenic differentiation in bone marrow mesenchymal stem cells (BMMSCs). We found that EtOH treatment led to the activation of the RIPK1/RIPK3/MLKL signaling, resulting in increased osteoblast necroptosis and decreased osteogenic differentiation and bone formation both in vivo and in vitro. We further discovered that excessive EtOH treatment-induced osteoblast necroptosis might partly depend on reactive oxygen species (ROS) generation; concomitantly, ROS contributed to necroptosis of osteoblasts through a positive feedback loop involving RIPK1/RIPK3. In addition, blocking of the RIPK1/RIPK3/MLKL signaling by necrostatin-1 (Nec-1), a key inhibitor of RIPK1 kinase in the necroptosis pathway, or antioxidant N-acetylcysteine (NAC), an inhibitor of ROS, could decrease the activation of osteoblast necroptosis and ameliorate alcohol-induced osteopenia both in vivo and in vitro. Collectively, we demonstrated that chronic high-dose alcohol consumption induced osteopenia via osteoblast necroptosis and revealed that RIPK1 kinase may be a therapeutic target for alcohol-induced osteopenia.Man GuoYong-Li HuangQi WuLi ChaiZong-Zhe JiangYan ZengSheng-Rong WanXiao-Zhen TanYang LongJun-Ling GuFang-Yuan TengYong XuHindawi LimitedarticleCytologyQH573-671ENOxidative Medicine and Cellular Longevity, Vol 2021 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Cytology QH573-671
spellingShingle	Cytology QH573-671 Man Guo Yong-Li Huang Qi Wu Li Chai Zong-Zhe Jiang Yan Zeng Sheng-Rong Wan Xiao-Zhen Tan Yang Long Jun-Ling Gu Fang-Yuan Teng Yong Xu Chronic Ethanol Consumption Induces Osteopenia via Activation of Osteoblast Necroptosis
description	Chronic high-dose alcohol consumption impairs bone remodeling, reduces bone mass, and increases the risk of osteoporosis and bone fracture. However, the mechanisms underlying alcohol-induced osteoporosis are yet to be elucidated. In this study, we showed that excess intake of ethyl alcohol (EtOH) resulted in osteopenia and osteoblast necroptosis in mice that led to necrotic lesions and reduced osteogenic differentiation in bone marrow mesenchymal stem cells (BMMSCs). We found that EtOH treatment led to the activation of the RIPK1/RIPK3/MLKL signaling, resulting in increased osteoblast necroptosis and decreased osteogenic differentiation and bone formation both in vivo and in vitro. We further discovered that excessive EtOH treatment-induced osteoblast necroptosis might partly depend on reactive oxygen species (ROS) generation; concomitantly, ROS contributed to necroptosis of osteoblasts through a positive feedback loop involving RIPK1/RIPK3. In addition, blocking of the RIPK1/RIPK3/MLKL signaling by necrostatin-1 (Nec-1), a key inhibitor of RIPK1 kinase in the necroptosis pathway, or antioxidant N-acetylcysteine (NAC), an inhibitor of ROS, could decrease the activation of osteoblast necroptosis and ameliorate alcohol-induced osteopenia both in vivo and in vitro. Collectively, we demonstrated that chronic high-dose alcohol consumption induced osteopenia via osteoblast necroptosis and revealed that RIPK1 kinase may be a therapeutic target for alcohol-induced osteopenia.
format	article
author	Man Guo Yong-Li Huang Qi Wu Li Chai Zong-Zhe Jiang Yan Zeng Sheng-Rong Wan Xiao-Zhen Tan Yang Long Jun-Ling Gu Fang-Yuan Teng Yong Xu
author_facet	Man Guo Yong-Li Huang Qi Wu Li Chai Zong-Zhe Jiang Yan Zeng Sheng-Rong Wan Xiao-Zhen Tan Yang Long Jun-Ling Gu Fang-Yuan Teng Yong Xu
author_sort	Man Guo
title	Chronic Ethanol Consumption Induces Osteopenia via Activation of Osteoblast Necroptosis
title_short	Chronic Ethanol Consumption Induces Osteopenia via Activation of Osteoblast Necroptosis
title_full	Chronic Ethanol Consumption Induces Osteopenia via Activation of Osteoblast Necroptosis
title_fullStr	Chronic Ethanol Consumption Induces Osteopenia via Activation of Osteoblast Necroptosis
title_full_unstemmed	Chronic Ethanol Consumption Induces Osteopenia via Activation of Osteoblast Necroptosis
title_sort	chronic ethanol consumption induces osteopenia via activation of osteoblast necroptosis
publisher	Hindawi Limited
publishDate	2021
url	https://doaj.org/article/f3b28d7747414e8bbe64aa2e9305badb
work_keys_str_mv	AT manguo chronicethanolconsumptioninducesosteopeniaviaactivationofosteoblastnecroptosis AT yonglihuang chronicethanolconsumptioninducesosteopeniaviaactivationofosteoblastnecroptosis AT qiwu chronicethanolconsumptioninducesosteopeniaviaactivationofosteoblastnecroptosis AT lichai chronicethanolconsumptioninducesosteopeniaviaactivationofosteoblastnecroptosis AT zongzhejiang chronicethanolconsumptioninducesosteopeniaviaactivationofosteoblastnecroptosis AT yanzeng chronicethanolconsumptioninducesosteopeniaviaactivationofosteoblastnecroptosis AT shengrongwan chronicethanolconsumptioninducesosteopeniaviaactivationofosteoblastnecroptosis AT xiaozhentan chronicethanolconsumptioninducesosteopeniaviaactivationofosteoblastnecroptosis AT yanglong chronicethanolconsumptioninducesosteopeniaviaactivationofosteoblastnecroptosis AT junlinggu chronicethanolconsumptioninducesosteopeniaviaactivationofosteoblastnecroptosis AT fangyuanteng chronicethanolconsumptioninducesosteopeniaviaactivationofosteoblastnecroptosis AT yongxu chronicethanolconsumptioninducesosteopeniaviaactivationofosteoblastnecroptosis
_version_	1718443246310391808

Chronic Ethanol Consumption Induces Osteopenia via Activation of Osteoblast Necroptosis

Ejemplares similares