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Dehydrocostus Lactone Attenuates the Senescence of Nucleus Pulposus Cells and Ameliorates Intervertebral Disc Degeneration via Inhibition of STING-TBK1/NF-κB and MAPK Signaling

The progression of intervertebral disc degeneration (IDD) is multifactorial with the senescence of nucleus pulposus (NP) cells and closely related to inflammation in NP cells. Dehydrocostus lactone (DHE) is a natural sesquiterpene lactone isolated from medicinal plants that has anti-inflammatory pro...

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Autores principales: Chen, Zhiqian, Yang, Xiao, Zhou, Yifan, Liang, Zhihao, Chen, Chen, Han, Chen, Cao, Xiankun, He, Wenxin, Zhang, Kai, Qin, An, Zhou, Tangjun, Zhao, Jie
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8079987/
https://www.ncbi.nlm.nih.gov/pubmed/33935734
http://dx.doi.org/10.3389/fphar.2021.641098
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author Chen, Zhiqian
Yang, Xiao
Zhou, Yifan
Liang, Zhihao
Chen, Chen
Han, Chen
Cao, Xiankun
He, Wenxin
Zhang, Kai
Qin, An
Zhou, Tangjun
Zhao, Jie
author_facet Chen, Zhiqian
Yang, Xiao
Zhou, Yifan
Liang, Zhihao
Chen, Chen
Han, Chen
Cao, Xiankun
He, Wenxin
Zhang, Kai
Qin, An
Zhou, Tangjun
Zhao, Jie
author_sort Chen, Zhiqian
collection PubMed
description The progression of intervertebral disc degeneration (IDD) is multifactorial with the senescence of nucleus pulposus (NP) cells and closely related to inflammation in NP cells. Dehydrocostus lactone (DHE) is a natural sesquiterpene lactone isolated from medicinal plants that has anti-inflammatory properties. Thus, DHE may have a therapeutic effect on the progression of IDD. In this study, NP cells were used to determine the appropriate concentration of DHE in vitro. The role of DHE in tumor necrosis factor-α (TNF-α)–induced activation of inflammatory signaling pathways and cellular senescence, together with anabolism and catabolism of extracellular matrix (ECM) in NP cells, was examined in vitro. The therapeutic effect of DHE in vivo was determined using a spinal instability model of IDD in mice. The TNF-α–induced ECM degradation and the senescence of NP cells were partially attenuated by DHE. Mechanistically, DHE inhibited the activation of NF-κB and MAPK inflammatory signaling pathways and ameliorated the senescence of NP cells caused by the activation of STING-TBK1/NF-κB signaling induced by TNF-α. Furthermore, a spinal instability model in mice demonstrated that DHE treatment could ameliorate progression of IDD. Together, our findings indicate that DHE can alleviate IDD changes and has a potential therapeutic function for the treatment of IDD.
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spelling pubmed-80799872021-04-29 Dehydrocostus Lactone Attenuates the Senescence of Nucleus Pulposus Cells and Ameliorates Intervertebral Disc Degeneration via Inhibition of STING-TBK1/NF-κB and MAPK Signaling Chen, Zhiqian Yang, Xiao Zhou, Yifan Liang, Zhihao Chen, Chen Han, Chen Cao, Xiankun He, Wenxin Zhang, Kai Qin, An Zhou, Tangjun Zhao, Jie Front Pharmacol Pharmacology The progression of intervertebral disc degeneration (IDD) is multifactorial with the senescence of nucleus pulposus (NP) cells and closely related to inflammation in NP cells. Dehydrocostus lactone (DHE) is a natural sesquiterpene lactone isolated from medicinal plants that has anti-inflammatory properties. Thus, DHE may have a therapeutic effect on the progression of IDD. In this study, NP cells were used to determine the appropriate concentration of DHE in vitro. The role of DHE in tumor necrosis factor-α (TNF-α)–induced activation of inflammatory signaling pathways and cellular senescence, together with anabolism and catabolism of extracellular matrix (ECM) in NP cells, was examined in vitro. The therapeutic effect of DHE in vivo was determined using a spinal instability model of IDD in mice. The TNF-α–induced ECM degradation and the senescence of NP cells were partially attenuated by DHE. Mechanistically, DHE inhibited the activation of NF-κB and MAPK inflammatory signaling pathways and ameliorated the senescence of NP cells caused by the activation of STING-TBK1/NF-κB signaling induced by TNF-α. Furthermore, a spinal instability model in mice demonstrated that DHE treatment could ameliorate progression of IDD. Together, our findings indicate that DHE can alleviate IDD changes and has a potential therapeutic function for the treatment of IDD. Frontiers Media S.A. 2021-04-14 /pmc/articles/PMC8079987/ /pubmed/33935734 http://dx.doi.org/10.3389/fphar.2021.641098 Text en Copyright © 2021 Chen, Yang, Zhou, Liang, Chen, Han, Cao, He, Zhang, Qin, Zhou and Zhao. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Chen, Zhiqian
Yang, Xiao
Zhou, Yifan
Liang, Zhihao
Chen, Chen
Han, Chen
Cao, Xiankun
He, Wenxin
Zhang, Kai
Qin, An
Zhou, Tangjun
Zhao, Jie
Dehydrocostus Lactone Attenuates the Senescence of Nucleus Pulposus Cells and Ameliorates Intervertebral Disc Degeneration via Inhibition of STING-TBK1/NF-κB and MAPK Signaling
title Dehydrocostus Lactone Attenuates the Senescence of Nucleus Pulposus Cells and Ameliorates Intervertebral Disc Degeneration via Inhibition of STING-TBK1/NF-κB and MAPK Signaling
title_full Dehydrocostus Lactone Attenuates the Senescence of Nucleus Pulposus Cells and Ameliorates Intervertebral Disc Degeneration via Inhibition of STING-TBK1/NF-κB and MAPK Signaling
title_fullStr Dehydrocostus Lactone Attenuates the Senescence of Nucleus Pulposus Cells and Ameliorates Intervertebral Disc Degeneration via Inhibition of STING-TBK1/NF-κB and MAPK Signaling
title_full_unstemmed Dehydrocostus Lactone Attenuates the Senescence of Nucleus Pulposus Cells and Ameliorates Intervertebral Disc Degeneration via Inhibition of STING-TBK1/NF-κB and MAPK Signaling
title_short Dehydrocostus Lactone Attenuates the Senescence of Nucleus Pulposus Cells and Ameliorates Intervertebral Disc Degeneration via Inhibition of STING-TBK1/NF-κB and MAPK Signaling
title_sort dehydrocostus lactone attenuates the senescence of nucleus pulposus cells and ameliorates intervertebral disc degeneration via inhibition of sting-tbk1/nf-κb and mapk signaling
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8079987/
https://www.ncbi.nlm.nih.gov/pubmed/33935734
http://dx.doi.org/10.3389/fphar.2021.641098
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