Dimethyl Fumarate Ameliorates Nucleus Pulposus Cell Dysfunction through Activating the Nrf2/HO-1 Pathway in Intervertebral Disc Degeneration

Background. Oxidative stress, inflammation, and nucleus pulposus cells (NPCs) apoptosis are involved in pathogenesis of intervertebral disc (IVD) degeneration (IVDD). Dimethyl fumarate (DMF) has been found to effectively depress oxidative stress and inflammation via the Nrf2 pathway. Hence, this pro...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Ruihong Wang, Dawei Luo, Zhiwei Li, Huimin Han
Formato:	article
Lenguaje:	EN
Publicado:	Hindawi Limited 2021
Materias:	Computer applications to medicine. Medical informatics R858-859.7
Acceso en línea:	https://doaj.org/article/e28a3a5b108942fdb65b322dcb56380f
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:e28a3a5b108942fdb65b322dcb56380f
record_format	dspace
spelling	oai:doaj.org-article:e28a3a5b108942fdb65b322dcb56380f2021-11-08T02:35:53ZDimethyl Fumarate Ameliorates Nucleus Pulposus Cell Dysfunction through Activating the Nrf2/HO-1 Pathway in Intervertebral Disc Degeneration1748-671810.1155/2021/6021763https://doaj.org/article/e28a3a5b108942fdb65b322dcb56380f2021-01-01T00:00:00Zhttp://dx.doi.org/10.1155/2021/6021763https://doaj.org/toc/1748-6718Background. Oxidative stress, inflammation, and nucleus pulposus cells (NPCs) apoptosis are involved in pathogenesis of intervertebral disc (IVD) degeneration (IVDD). Dimethyl fumarate (DMF) has been found to effectively depress oxidative stress and inflammation via the Nrf2 pathway. Hence, this project was designed to explore the underlying mechanisms of how DMF protects NPCs from damage by LPS challenge. Methods and Results. CCK8 assay and flow cytometry of apoptosis indicated that DMF treatment attenuated LPS-induced NPC damage. Western blot analysis demonstrated that DMF enhanced the expressions of nuclear factor-erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) in LPS-challenged NPCs. DMF treatment significantly decreased the accumulation of ROS, downregulated inflammatory cytokines (p-NF-κB, IL-1β, and TNF-α), and ER stress-associated apoptosis proteins (Bip, calpain-1, caspase-12, caspase-3, and Bax) in LPS-challenged NPCs. The level of antiapoptotic protein Bcl-2 was promoted by DMF treatment in LPS-challenged NPCs. Glutathione (GSH) assay showed that DMF treatment improved reduced to oxidized glutathione ratio in LPS-challenged NPCs. Furthermore, the results of western blot analysis indicated that in LPS-challenged NPCs, DMF treatment ameliorated the elevated levels of matrix degradation enzymes (MMP-13, aggrecanase 1) and type I collagen and the reduced levels of matrix composition (type II collagen and ACAN). However, Nrf2 knockdown abolished these protective effects of DMF. Conclusion. Our data suggested that treatment with DMF mitigated LPS-induced oxidative stress, inflammation, and ER stress-associated apoptosis in NPCs via the Nrf2/HO-1 signaling pathway, thus reliving LPS-induced dysfunction of NPCs, which offered a novel potential pharmacological treatment strategy for IVDD.Ruihong WangDawei LuoZhiwei LiHuimin HanHindawi LimitedarticleComputer applications to medicine. Medical informaticsR858-859.7ENComputational and Mathematical Methods in Medicine, Vol 2021 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Computer applications to medicine. Medical informatics R858-859.7
spellingShingle	Computer applications to medicine. Medical informatics R858-859.7 Ruihong Wang Dawei Luo Zhiwei Li Huimin Han Dimethyl Fumarate Ameliorates Nucleus Pulposus Cell Dysfunction through Activating the Nrf2/HO-1 Pathway in Intervertebral Disc Degeneration
description	Background. Oxidative stress, inflammation, and nucleus pulposus cells (NPCs) apoptosis are involved in pathogenesis of intervertebral disc (IVD) degeneration (IVDD). Dimethyl fumarate (DMF) has been found to effectively depress oxidative stress and inflammation via the Nrf2 pathway. Hence, this project was designed to explore the underlying mechanisms of how DMF protects NPCs from damage by LPS challenge. Methods and Results. CCK8 assay and flow cytometry of apoptosis indicated that DMF treatment attenuated LPS-induced NPC damage. Western blot analysis demonstrated that DMF enhanced the expressions of nuclear factor-erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) in LPS-challenged NPCs. DMF treatment significantly decreased the accumulation of ROS, downregulated inflammatory cytokines (p-NF-κB, IL-1β, and TNF-α), and ER stress-associated apoptosis proteins (Bip, calpain-1, caspase-12, caspase-3, and Bax) in LPS-challenged NPCs. The level of antiapoptotic protein Bcl-2 was promoted by DMF treatment in LPS-challenged NPCs. Glutathione (GSH) assay showed that DMF treatment improved reduced to oxidized glutathione ratio in LPS-challenged NPCs. Furthermore, the results of western blot analysis indicated that in LPS-challenged NPCs, DMF treatment ameliorated the elevated levels of matrix degradation enzymes (MMP-13, aggrecanase 1) and type I collagen and the reduced levels of matrix composition (type II collagen and ACAN). However, Nrf2 knockdown abolished these protective effects of DMF. Conclusion. Our data suggested that treatment with DMF mitigated LPS-induced oxidative stress, inflammation, and ER stress-associated apoptosis in NPCs via the Nrf2/HO-1 signaling pathway, thus reliving LPS-induced dysfunction of NPCs, which offered a novel potential pharmacological treatment strategy for IVDD.
format	article
author	Ruihong Wang Dawei Luo Zhiwei Li Huimin Han
author_facet	Ruihong Wang Dawei Luo Zhiwei Li Huimin Han
author_sort	Ruihong Wang
title	Dimethyl Fumarate Ameliorates Nucleus Pulposus Cell Dysfunction through Activating the Nrf2/HO-1 Pathway in Intervertebral Disc Degeneration
title_short	Dimethyl Fumarate Ameliorates Nucleus Pulposus Cell Dysfunction through Activating the Nrf2/HO-1 Pathway in Intervertebral Disc Degeneration
title_full	Dimethyl Fumarate Ameliorates Nucleus Pulposus Cell Dysfunction through Activating the Nrf2/HO-1 Pathway in Intervertebral Disc Degeneration
title_fullStr	Dimethyl Fumarate Ameliorates Nucleus Pulposus Cell Dysfunction through Activating the Nrf2/HO-1 Pathway in Intervertebral Disc Degeneration
title_full_unstemmed	Dimethyl Fumarate Ameliorates Nucleus Pulposus Cell Dysfunction through Activating the Nrf2/HO-1 Pathway in Intervertebral Disc Degeneration
title_sort	dimethyl fumarate ameliorates nucleus pulposus cell dysfunction through activating the nrf2/ho-1 pathway in intervertebral disc degeneration
publisher	Hindawi Limited
publishDate	2021
url	https://doaj.org/article/e28a3a5b108942fdb65b322dcb56380f
work_keys_str_mv	AT ruihongwang dimethylfumarateamelioratesnucleuspulposuscelldysfunctionthroughactivatingthenrf2ho1pathwayinintervertebraldiscdegeneration AT daweiluo dimethylfumarateamelioratesnucleuspulposuscelldysfunctionthroughactivatingthenrf2ho1pathwayinintervertebraldiscdegeneration AT zhiweili dimethylfumarateamelioratesnucleuspulposuscelldysfunctionthroughactivatingthenrf2ho1pathwayinintervertebraldiscdegeneration AT huiminhan dimethylfumarateamelioratesnucleuspulposuscelldysfunctionthroughactivatingthenrf2ho1pathwayinintervertebraldiscdegeneration
_version_	1718443238888570880

Dimethyl Fumarate Ameliorates Nucleus Pulposus Cell Dysfunction through Activating the Nrf2/HO-1 Pathway in Intervertebral Disc Degeneration

Ejemplares similares