Semaphorin 3A mitigates lipopolysaccharide-induced chondrocyte inflammation, apoptosis and extracellular matrix degradation by binding to Neuropilin-1

Semaphorin 3A (SEMA3A) and its receptor neuropilin-1 (NRP-1) are expressed low in chondrocytes under stress, and overexpressing SEMA3A reduces pro-inflammatory cytokine release. This study was aimed at exploring whether SEMA3A participates in lipopolysaccharide (LPS)-induced chondrocyte inflammation...

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Autores principales: Huiyu Zhang, Yue Lu, BingBing Wu, Fei Xia
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Lenguaje:EN
Publicado: Taylor & Francis Group 2021
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Acceso en línea:https://doaj.org/article/c02d831afe32491c914f6ea35536d584
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spelling oai:doaj.org-article:c02d831afe32491c914f6ea35536d5842021-11-26T11:19:49ZSemaphorin 3A mitigates lipopolysaccharide-induced chondrocyte inflammation, apoptosis and extracellular matrix degradation by binding to Neuropilin-12165-59792165-598710.1080/21655979.2021.1974806https://doaj.org/article/c02d831afe32491c914f6ea35536d5842021-12-01T00:00:00Zhttp://dx.doi.org/10.1080/21655979.2021.1974806https://doaj.org/toc/2165-5979https://doaj.org/toc/2165-5987Semaphorin 3A (SEMA3A) and its receptor neuropilin-1 (NRP-1) are expressed low in chondrocytes under stress, and overexpressing SEMA3A reduces pro-inflammatory cytokine release. This study was aimed at exploring whether SEMA3A participates in lipopolysaccharide (LPS)-induced chondrocyte inflammation, apoptosis and extracellular matrix (ECM) degradation. SEMA3A and NRP-1 expression in LPS-induced ATDC5 cells was determined with RT-qPCR and western blotting. Following stimulation with LPS in the absence or presence of SEMA3A overexpression, the viability of ATDC5 cells was observed through CCK-8 assay. RT-qPCR and western blot were performed to detect the expression of pro-inflammatory cytokines. ATDC5 cell apoptosis was observed through TUNEL, and apoptosis-related proteins were assayed. Expression of ECM-related proteins was measured by RT-qPCR and western blotting. Additionally, the binding of SEMA3A to NRP-1 was verified by co-immunoprecipitation. After interference with NRP-1, cell viability, inflammation and ECM degradation were examined in LPS-induced ATDC5 cells with SEMA3A overexpression. Results revealed that SEMA3A expression in ATDC5 cells decreased following stimulation with LPS. Overexpressing SEMA3A improved cell viability and reduced the inflammatory injury of LPS-stimulated ATDC5 cells. Moreover, SEMA3A overexpression alleviated LPS-induced apoptosis and ECM degradation of ATDC5 chondrocytes. SEMA3A and NRP-1 bound to each other in ATDC5 cells. NRP-1 interference crippled the ameliorative effect of SEMA3A overexpression on LPS-induced chondrocyte inflammation, apoptosis and ECM degradation. To conclude, SEMA3A binds to NRP-1, mitigating LPS-induced chondrocyte inflammation, apoptosis and ECM degradation. This study elucidated the role of SEMA3A in osteoarthritis and illustrated its action mechanism involving NRP-1.Huiyu ZhangYue LuBingBing WuFei XiaTaylor & Francis Grouparticlesema3anrp-1chondrocyte apoptosisextracellular matrix degradationosteoarthritisBiotechnologyTP248.13-248.65ENBioengineered, Vol 12, Iss 2, Pp 9641-9654 (2021)
institution DOAJ
collection DOAJ
language EN
topic sema3a
nrp-1
chondrocyte apoptosis
extracellular matrix degradation
osteoarthritis
Biotechnology
TP248.13-248.65
spellingShingle sema3a
nrp-1
chondrocyte apoptosis
extracellular matrix degradation
osteoarthritis
Biotechnology
TP248.13-248.65
Huiyu Zhang
Yue Lu
BingBing Wu
Fei Xia
Semaphorin 3A mitigates lipopolysaccharide-induced chondrocyte inflammation, apoptosis and extracellular matrix degradation by binding to Neuropilin-1
description Semaphorin 3A (SEMA3A) and its receptor neuropilin-1 (NRP-1) are expressed low in chondrocytes under stress, and overexpressing SEMA3A reduces pro-inflammatory cytokine release. This study was aimed at exploring whether SEMA3A participates in lipopolysaccharide (LPS)-induced chondrocyte inflammation, apoptosis and extracellular matrix (ECM) degradation. SEMA3A and NRP-1 expression in LPS-induced ATDC5 cells was determined with RT-qPCR and western blotting. Following stimulation with LPS in the absence or presence of SEMA3A overexpression, the viability of ATDC5 cells was observed through CCK-8 assay. RT-qPCR and western blot were performed to detect the expression of pro-inflammatory cytokines. ATDC5 cell apoptosis was observed through TUNEL, and apoptosis-related proteins were assayed. Expression of ECM-related proteins was measured by RT-qPCR and western blotting. Additionally, the binding of SEMA3A to NRP-1 was verified by co-immunoprecipitation. After interference with NRP-1, cell viability, inflammation and ECM degradation were examined in LPS-induced ATDC5 cells with SEMA3A overexpression. Results revealed that SEMA3A expression in ATDC5 cells decreased following stimulation with LPS. Overexpressing SEMA3A improved cell viability and reduced the inflammatory injury of LPS-stimulated ATDC5 cells. Moreover, SEMA3A overexpression alleviated LPS-induced apoptosis and ECM degradation of ATDC5 chondrocytes. SEMA3A and NRP-1 bound to each other in ATDC5 cells. NRP-1 interference crippled the ameliorative effect of SEMA3A overexpression on LPS-induced chondrocyte inflammation, apoptosis and ECM degradation. To conclude, SEMA3A binds to NRP-1, mitigating LPS-induced chondrocyte inflammation, apoptosis and ECM degradation. This study elucidated the role of SEMA3A in osteoarthritis and illustrated its action mechanism involving NRP-1.
format article
author Huiyu Zhang
Yue Lu
BingBing Wu
Fei Xia
author_facet Huiyu Zhang
Yue Lu
BingBing Wu
Fei Xia
author_sort Huiyu Zhang
title Semaphorin 3A mitigates lipopolysaccharide-induced chondrocyte inflammation, apoptosis and extracellular matrix degradation by binding to Neuropilin-1
title_short Semaphorin 3A mitigates lipopolysaccharide-induced chondrocyte inflammation, apoptosis and extracellular matrix degradation by binding to Neuropilin-1
title_full Semaphorin 3A mitigates lipopolysaccharide-induced chondrocyte inflammation, apoptosis and extracellular matrix degradation by binding to Neuropilin-1
title_fullStr Semaphorin 3A mitigates lipopolysaccharide-induced chondrocyte inflammation, apoptosis and extracellular matrix degradation by binding to Neuropilin-1
title_full_unstemmed Semaphorin 3A mitigates lipopolysaccharide-induced chondrocyte inflammation, apoptosis and extracellular matrix degradation by binding to Neuropilin-1
title_sort semaphorin 3a mitigates lipopolysaccharide-induced chondrocyte inflammation, apoptosis and extracellular matrix degradation by binding to neuropilin-1
publisher Taylor & Francis Group
publishDate 2021
url https://doaj.org/article/c02d831afe32491c914f6ea35536d584
work_keys_str_mv AT huiyuzhang semaphorin3amitigateslipopolysaccharideinducedchondrocyteinflammationapoptosisandextracellularmatrixdegradationbybindingtoneuropilin1
AT yuelu semaphorin3amitigateslipopolysaccharideinducedchondrocyteinflammationapoptosisandextracellularmatrixdegradationbybindingtoneuropilin1
AT bingbingwu semaphorin3amitigateslipopolysaccharideinducedchondrocyteinflammationapoptosisandextracellularmatrixdegradationbybindingtoneuropilin1
AT feixia semaphorin3amitigateslipopolysaccharideinducedchondrocyteinflammationapoptosisandextracellularmatrixdegradationbybindingtoneuropilin1
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