ERα-Targeting PROTAC as a Chemical Knockdown Tool to Investigate the Estrogen Receptor Function in Rat Menopausal Arthritis

Proteolytic targeting chimeras (PROTACs) is a rapid and reversible chemical knockout method. Compared with traditional gene-editing tools, it can avoid potential genetic compensation, misunderstandings caused by spontaneous mutations, or gene knockouts that lead to embryonic death. To study the role...

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Autores principales:	Li Duan, Xiao Xu, Limei Xu, Caining Wen, Kan Ouyang, Zigang Li, Yujie Liang
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	PROTACs estrogen receptor α MMP-13 articular cartilage metabolism menopausal arthritis Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/d450ca4837e340d995e0a2b61ba8edd1
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spelling	oai:doaj.org-article:d450ca4837e340d995e0a2b61ba8edd12021-12-01T19:02:51ZERα-Targeting PROTAC as a Chemical Knockdown Tool to Investigate the Estrogen Receptor Function in Rat Menopausal Arthritis1663-981210.3389/fphar.2021.764154https://doaj.org/article/d450ca4837e340d995e0a2b61ba8edd12021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fphar.2021.764154/fullhttps://doaj.org/toc/1663-9812Proteolytic targeting chimeras (PROTACs) is a rapid and reversible chemical knockout method. Compared with traditional gene-editing tools, it can avoid potential genetic compensation, misunderstandings caused by spontaneous mutations, or gene knockouts that lead to embryonic death. To study the role of estrogen receptor alpha (ERα) in the occurrence and progression of menopausal arthritis, we report a chemical knockout strategy in which stable peptide-based (PROTACs) against ERα to inhibit their function. This chemical knockdown strategy can effectively and quickly inhibit ERα protein in vivo and in vitro. In the rat menopausal arthritis model, this study showed that inhibiting estrogen function by degrading ERα can significantly interfere with cartilage matrix metabolism and cause menopausal arthritis by up-regulating matrix metalloproteinase (MMP-13). The results of this study indicate that ERα is a crucial estrogen receptor for maintaining cartilage metabolism. Inhibition of ERα function by PROTACs can promote the progression of osteoarthritis.Li DuanXiao XuLimei XuCaining WenKan OuyangZigang LiYujie LiangFrontiers Media S.A.articlePROTACsestrogen receptor αMMP-13articular cartilage metabolismmenopausal arthritisTherapeutics. PharmacologyRM1-950ENFrontiers in Pharmacology, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	PROTACs estrogen receptor α MMP-13 articular cartilage metabolism menopausal arthritis Therapeutics. Pharmacology RM1-950
spellingShingle	PROTACs estrogen receptor α MMP-13 articular cartilage metabolism menopausal arthritis Therapeutics. Pharmacology RM1-950 Li Duan Xiao Xu Limei Xu Caining Wen Kan Ouyang Zigang Li Yujie Liang ERα-Targeting PROTAC as a Chemical Knockdown Tool to Investigate the Estrogen Receptor Function in Rat Menopausal Arthritis
description	Proteolytic targeting chimeras (PROTACs) is a rapid and reversible chemical knockout method. Compared with traditional gene-editing tools, it can avoid potential genetic compensation, misunderstandings caused by spontaneous mutations, or gene knockouts that lead to embryonic death. To study the role of estrogen receptor alpha (ERα) in the occurrence and progression of menopausal arthritis, we report a chemical knockout strategy in which stable peptide-based (PROTACs) against ERα to inhibit their function. This chemical knockdown strategy can effectively and quickly inhibit ERα protein in vivo and in vitro. In the rat menopausal arthritis model, this study showed that inhibiting estrogen function by degrading ERα can significantly interfere with cartilage matrix metabolism and cause menopausal arthritis by up-regulating matrix metalloproteinase (MMP-13). The results of this study indicate that ERα is a crucial estrogen receptor for maintaining cartilage metabolism. Inhibition of ERα function by PROTACs can promote the progression of osteoarthritis.
format	article
author	Li Duan Xiao Xu Limei Xu Caining Wen Kan Ouyang Zigang Li Yujie Liang
author_facet	Li Duan Xiao Xu Limei Xu Caining Wen Kan Ouyang Zigang Li Yujie Liang
author_sort	Li Duan
title	ERα-Targeting PROTAC as a Chemical Knockdown Tool to Investigate the Estrogen Receptor Function in Rat Menopausal Arthritis
title_short	ERα-Targeting PROTAC as a Chemical Knockdown Tool to Investigate the Estrogen Receptor Function in Rat Menopausal Arthritis
title_full	ERα-Targeting PROTAC as a Chemical Knockdown Tool to Investigate the Estrogen Receptor Function in Rat Menopausal Arthritis
title_fullStr	ERα-Targeting PROTAC as a Chemical Knockdown Tool to Investigate the Estrogen Receptor Function in Rat Menopausal Arthritis
title_full_unstemmed	ERα-Targeting PROTAC as a Chemical Knockdown Tool to Investigate the Estrogen Receptor Function in Rat Menopausal Arthritis
title_sort	erα-targeting protac as a chemical knockdown tool to investigate the estrogen receptor function in rat menopausal arthritis
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/d450ca4837e340d995e0a2b61ba8edd1
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ERα-Targeting PROTAC as a Chemical Knockdown Tool to Investigate the Estrogen Receptor Function in Rat Menopausal Arthritis

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