Physalin A Inhibits MAPK and NF-κB Signal Transduction Through Integrin αVβ3 and Exerts Chondroprotective Effect

Osteoarthritis (OA) is a common articular ailment presented with cartilage loss and destruction that is common observed in the elderly population. Physalin A (PA), a natural bioactive withanolide, exerts anti-inflammatory residences in more than a few diseases; however, little is known about its eff...

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Autores principales:	Rui Lu, Xiaojun Yu, Shuang Liang, Peng Cheng, Zhenggang Wang, Zhi-yi He, Zheng-tao Lv, Junlai Wan, Haokun Mo, Wen-tao Zhu, An-min Chen
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	physalin A osteoarthritis αvβ3 integrin MAPK NF-κB Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/5d54d14db65347bc9eadb532e5e27062
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spelling	oai:doaj.org-article:5d54d14db65347bc9eadb532e5e270622021-12-02T15:48:09ZPhysalin A Inhibits MAPK and NF-κB Signal Transduction Through Integrin αVβ3 and Exerts Chondroprotective Effect1663-981210.3389/fphar.2021.761922https://doaj.org/article/5d54d14db65347bc9eadb532e5e270622021-12-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fphar.2021.761922/fullhttps://doaj.org/toc/1663-9812Osteoarthritis (OA) is a common articular ailment presented with cartilage loss and destruction that is common observed in the elderly population. Physalin A (PA), a natural bioactive withanolide, exerts anti-inflammatory residences in more than a few diseases; however, little is known about its efficacy for OA treatment. Here, we explored the therapeutic effects and potential mechanism of PA in mouse OA. After the in vitro administration of PA, the expression of inflammation indicators including inducible nitric oxide synthase and cyclooxygenase-2 was low, indicating that PA could alleviate the IL-1β-induced chondrocyte inflammation response. Moreover, PA reduced IL-1β-induced destruction of the extracellular matrix by upregulating the gene expression of anabolism factors, including collagen II, aggrecan, and sry-box transcription factor 9, and downregulating the gene expression of catabolic factors, including thrombospondin motif 5 and matrix metalloproteinases. In addition, the chondroprotective effect of PA was credited to the inhibition of mitogen-activated protein kinase (MAPK) and nuclear factor-κB (NF-κB) signaling pathways. Furthermore, in vivo experiments showed that intra-articular injection of PA could alleviate cartilage destruction in a mouse OA model. However, the anti-inflammatory, anabolism enhancing, catabolism inhibiting, and MAPK and NF-κB signaling pathway inhibiting properties of PA on IL-1β-induced chondrocytes could be reversed when integrin αVβ3 is knocked down by siRNA. In conclusion, our work demonstrates that PA exhibits a chondroprotective effect that may be mediated by integrin αVβ3. Thus, PA or integrin αVβ3 might be a promising agent or molecular target for the treatment of OA.Rui LuXiaojun YuShuang LiangPeng ChengZhenggang WangZhenggang WangZhi-yi HeZheng-tao LvJunlai WanHaokun MoWen-tao ZhuAn-min ChenFrontiers Media S.A.articlephysalin Aosteoarthritisαvβ3integrinMAPKNF-κBTherapeutics. PharmacologyRM1-950ENFrontiers in Pharmacology, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	physalin A osteoarthritis αvβ3 integrin MAPK NF-κB Therapeutics. Pharmacology RM1-950
spellingShingle	physalin A osteoarthritis αvβ3 integrin MAPK NF-κB Therapeutics. Pharmacology RM1-950 Rui Lu Xiaojun Yu Shuang Liang Peng Cheng Zhenggang Wang Zhenggang Wang Zhi-yi He Zheng-tao Lv Junlai Wan Haokun Mo Wen-tao Zhu An-min Chen Physalin A Inhibits MAPK and NF-κB Signal Transduction Through Integrin αVβ3 and Exerts Chondroprotective Effect
description	Osteoarthritis (OA) is a common articular ailment presented with cartilage loss and destruction that is common observed in the elderly population. Physalin A (PA), a natural bioactive withanolide, exerts anti-inflammatory residences in more than a few diseases; however, little is known about its efficacy for OA treatment. Here, we explored the therapeutic effects and potential mechanism of PA in mouse OA. After the in vitro administration of PA, the expression of inflammation indicators including inducible nitric oxide synthase and cyclooxygenase-2 was low, indicating that PA could alleviate the IL-1β-induced chondrocyte inflammation response. Moreover, PA reduced IL-1β-induced destruction of the extracellular matrix by upregulating the gene expression of anabolism factors, including collagen II, aggrecan, and sry-box transcription factor 9, and downregulating the gene expression of catabolic factors, including thrombospondin motif 5 and matrix metalloproteinases. In addition, the chondroprotective effect of PA was credited to the inhibition of mitogen-activated protein kinase (MAPK) and nuclear factor-κB (NF-κB) signaling pathways. Furthermore, in vivo experiments showed that intra-articular injection of PA could alleviate cartilage destruction in a mouse OA model. However, the anti-inflammatory, anabolism enhancing, catabolism inhibiting, and MAPK and NF-κB signaling pathway inhibiting properties of PA on IL-1β-induced chondrocytes could be reversed when integrin αVβ3 is knocked down by siRNA. In conclusion, our work demonstrates that PA exhibits a chondroprotective effect that may be mediated by integrin αVβ3. Thus, PA or integrin αVβ3 might be a promising agent or molecular target for the treatment of OA.
format	article
author	Rui Lu Xiaojun Yu Shuang Liang Peng Cheng Zhenggang Wang Zhenggang Wang Zhi-yi He Zheng-tao Lv Junlai Wan Haokun Mo Wen-tao Zhu An-min Chen
author_facet	Rui Lu Xiaojun Yu Shuang Liang Peng Cheng Zhenggang Wang Zhenggang Wang Zhi-yi He Zheng-tao Lv Junlai Wan Haokun Mo Wen-tao Zhu An-min Chen
author_sort	Rui Lu
title	Physalin A Inhibits MAPK and NF-κB Signal Transduction Through Integrin αVβ3 and Exerts Chondroprotective Effect
title_short	Physalin A Inhibits MAPK and NF-κB Signal Transduction Through Integrin αVβ3 and Exerts Chondroprotective Effect
title_full	Physalin A Inhibits MAPK and NF-κB Signal Transduction Through Integrin αVβ3 and Exerts Chondroprotective Effect
title_fullStr	Physalin A Inhibits MAPK and NF-κB Signal Transduction Through Integrin αVβ3 and Exerts Chondroprotective Effect
title_full_unstemmed	Physalin A Inhibits MAPK and NF-κB Signal Transduction Through Integrin αVβ3 and Exerts Chondroprotective Effect
title_sort	physalin a inhibits mapk and nf-κb signal transduction through integrin αvβ3 and exerts chondroprotective effect
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/5d54d14db65347bc9eadb532e5e27062
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Physalin A Inhibits MAPK and NF-κB Signal Transduction Through Integrin αVβ3 and Exerts Chondroprotective Effect

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