Wnt7b Inhibits Osteoclastogenesis via AKT Activation and Glucose Metabolic Rewiring

The imbalance between bone formation and bone resorption causes osteoporosis, which leads to severe bone fractures. It is known that increases in osteoclast numbers and activities are the main reasons for increasing bone resorption. Although extensive studies have investigated the regulation of oste...

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Autores principales:	Fanzi Wu, Boer Li, Xuchen Hu, Fanyuan Yu, Yu Shi, Ling Ye
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	Wnt7b osteoclastogenesis AKT glucose metabolism osteoporosis Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/88aaefed3a2b467fa561c0d5901f24fe
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spelling	oai:doaj.org-article:88aaefed3a2b467fa561c0d5901f24fe2021-11-22T06:11:58ZWnt7b Inhibits Osteoclastogenesis via AKT Activation and Glucose Metabolic Rewiring2296-634X10.3389/fcell.2021.771336https://doaj.org/article/88aaefed3a2b467fa561c0d5901f24fe2021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fcell.2021.771336/fullhttps://doaj.org/toc/2296-634XThe imbalance between bone formation and bone resorption causes osteoporosis, which leads to severe bone fractures. It is known that increases in osteoclast numbers and activities are the main reasons for increasing bone resorption. Although extensive studies have investigated the regulation of osteoclastogenesis of bone marrow macrophages (BMMs), new pharmacological avenues still need to be unveiled for clinical purpose. Wnt ligands have been widely demonstrated as stimulators of bone formation; however, the inhibitory effect of the Wnt pathway in osteoclastogenesis is largely unknown. Here, we demonstrate that Wnt7b, a potent Wnt ligand that enhances bone formation and increases bone mass, also abolishes osteoclastogenesis in vitro. Importantly, enforced expression of Wnt in bone marrow macrophage lineage cells significantly disrupts osteoclast formation and activity, which leads to a dramatic increase in bone mass. Mechanistically, Wnt7b impacts the glucose metabolic process and AKT activation during osteoclastogenesis. Thus, we demonstrate that Wnt7b diminishes osteoclast formation, which will be beneficial for osteoporosis therapy in the future.Fanzi WuBoer LiBoer LiXuchen HuXuchen HuFanyuan YuFanyuan YuYu ShiLing YeLing YeFrontiers Media S.A.articleWnt7bosteoclastogenesisAKTglucose metabolismosteoporosisBiology (General)QH301-705.5ENFrontiers in Cell and Developmental Biology, Vol 9 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Wnt7b osteoclastogenesis AKT glucose metabolism osteoporosis Biology (General) QH301-705.5
spellingShingle	Wnt7b osteoclastogenesis AKT glucose metabolism osteoporosis Biology (General) QH301-705.5 Fanzi Wu Boer Li Boer Li Xuchen Hu Xuchen Hu Fanyuan Yu Fanyuan Yu Yu Shi Ling Ye Ling Ye Wnt7b Inhibits Osteoclastogenesis via AKT Activation and Glucose Metabolic Rewiring
description	The imbalance between bone formation and bone resorption causes osteoporosis, which leads to severe bone fractures. It is known that increases in osteoclast numbers and activities are the main reasons for increasing bone resorption. Although extensive studies have investigated the regulation of osteoclastogenesis of bone marrow macrophages (BMMs), new pharmacological avenues still need to be unveiled for clinical purpose. Wnt ligands have been widely demonstrated as stimulators of bone formation; however, the inhibitory effect of the Wnt pathway in osteoclastogenesis is largely unknown. Here, we demonstrate that Wnt7b, a potent Wnt ligand that enhances bone formation and increases bone mass, also abolishes osteoclastogenesis in vitro. Importantly, enforced expression of Wnt in bone marrow macrophage lineage cells significantly disrupts osteoclast formation and activity, which leads to a dramatic increase in bone mass. Mechanistically, Wnt7b impacts the glucose metabolic process and AKT activation during osteoclastogenesis. Thus, we demonstrate that Wnt7b diminishes osteoclast formation, which will be beneficial for osteoporosis therapy in the future.
format	article
author	Fanzi Wu Boer Li Boer Li Xuchen Hu Xuchen Hu Fanyuan Yu Fanyuan Yu Yu Shi Ling Ye Ling Ye
author_facet	Fanzi Wu Boer Li Boer Li Xuchen Hu Xuchen Hu Fanyuan Yu Fanyuan Yu Yu Shi Ling Ye Ling Ye
author_sort	Fanzi Wu
title	Wnt7b Inhibits Osteoclastogenesis via AKT Activation and Glucose Metabolic Rewiring
title_short	Wnt7b Inhibits Osteoclastogenesis via AKT Activation and Glucose Metabolic Rewiring
title_full	Wnt7b Inhibits Osteoclastogenesis via AKT Activation and Glucose Metabolic Rewiring
title_fullStr	Wnt7b Inhibits Osteoclastogenesis via AKT Activation and Glucose Metabolic Rewiring
title_full_unstemmed	Wnt7b Inhibits Osteoclastogenesis via AKT Activation and Glucose Metabolic Rewiring
title_sort	wnt7b inhibits osteoclastogenesis via akt activation and glucose metabolic rewiring
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/88aaefed3a2b467fa561c0d5901f24fe
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Wnt7b Inhibits Osteoclastogenesis via AKT Activation and Glucose Metabolic Rewiring

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