Elevated inflammatory gene expression in intervertebral disc tissues in mice with ADAM8 inactivated

Abstract We found ADAM8 enzymatic activity elevated in degenerative human intervertebral disc (IVD). Here, we examined the discs in ADAM8-inactivation mice that carry a mutation preventing self-activation of the enzyme. Surprisingly, elevated gene expression for inflammatory markers (Cxcl1, IL6) was...

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Autores principales:	Yejia Zhang, Zuozhen Tian, David Gerard, Lutian Yao, Frances S. Shofer, Gabriella Cs-Szabo, Ling Qin, Maurizio Pacifici, Motomi Enomoto-Iwamoto
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/29482a7dd36f42fc82304c841792897b
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spelling	oai:doaj.org-article:29482a7dd36f42fc82304c841792897b2021-12-02T14:09:02ZElevated inflammatory gene expression in intervertebral disc tissues in mice with ADAM8 inactivated10.1038/s41598-021-81495-y2045-2322https://doaj.org/article/29482a7dd36f42fc82304c841792897b2021-01-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-81495-yhttps://doaj.org/toc/2045-2322Abstract We found ADAM8 enzymatic activity elevated in degenerative human intervertebral disc (IVD). Here, we examined the discs in ADAM8-inactivation mice that carry a mutation preventing self-activation of the enzyme. Surprisingly, elevated gene expression for inflammatory markers (Cxcl1, IL6) was observed in injured discs of ADAM8 mutant mice, along with elevated expression of type 2 collagen gene (Col2a1), compared with wild type controls. Injured annulus fibrosus of mutant and wild type mice contained a higher proportion of large collagen fibers compared with intact discs, as documented by microscopic examination under circular polarized light. In the intact IVDs, Adam8 EQ mouse AF contained lower proportion of yellow (intermediate) fiber than WT mice. This suggests that ADAM8 may regulate inflammation and collagen fiber assembly. The seemingly contradictory findings of elevated inflammatory markers in mutant mice and excessive ADAM8 activity in human degenerative discs suggest that ADAM8 may interact with other enzymatic and pro-inflammatory processes needed for tissue maintenance and repair. As a future therapeutic intervention to retard intervertebral disc degeneration, partial inhibition of ADAM8 proteolysis may be more desirable than complete inactivation of this enzyme.Yejia ZhangZuozhen TianDavid GerardLutian YaoFrances S. ShoferGabriella Cs-SzaboLing QinMaurizio PacificiMotomi Enomoto-IwamotoNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Yejia Zhang Zuozhen Tian David Gerard Lutian Yao Frances S. Shofer Gabriella Cs-Szabo Ling Qin Maurizio Pacifici Motomi Enomoto-Iwamoto Elevated inflammatory gene expression in intervertebral disc tissues in mice with ADAM8 inactivated
description	Abstract We found ADAM8 enzymatic activity elevated in degenerative human intervertebral disc (IVD). Here, we examined the discs in ADAM8-inactivation mice that carry a mutation preventing self-activation of the enzyme. Surprisingly, elevated gene expression for inflammatory markers (Cxcl1, IL6) was observed in injured discs of ADAM8 mutant mice, along with elevated expression of type 2 collagen gene (Col2a1), compared with wild type controls. Injured annulus fibrosus of mutant and wild type mice contained a higher proportion of large collagen fibers compared with intact discs, as documented by microscopic examination under circular polarized light. In the intact IVDs, Adam8 EQ mouse AF contained lower proportion of yellow (intermediate) fiber than WT mice. This suggests that ADAM8 may regulate inflammation and collagen fiber assembly. The seemingly contradictory findings of elevated inflammatory markers in mutant mice and excessive ADAM8 activity in human degenerative discs suggest that ADAM8 may interact with other enzymatic and pro-inflammatory processes needed for tissue maintenance and repair. As a future therapeutic intervention to retard intervertebral disc degeneration, partial inhibition of ADAM8 proteolysis may be more desirable than complete inactivation of this enzyme.
format	article
author	Yejia Zhang Zuozhen Tian David Gerard Lutian Yao Frances S. Shofer Gabriella Cs-Szabo Ling Qin Maurizio Pacifici Motomi Enomoto-Iwamoto
author_facet	Yejia Zhang Zuozhen Tian David Gerard Lutian Yao Frances S. Shofer Gabriella Cs-Szabo Ling Qin Maurizio Pacifici Motomi Enomoto-Iwamoto
author_sort	Yejia Zhang
title	Elevated inflammatory gene expression in intervertebral disc tissues in mice with ADAM8 inactivated
title_short	Elevated inflammatory gene expression in intervertebral disc tissues in mice with ADAM8 inactivated
title_full	Elevated inflammatory gene expression in intervertebral disc tissues in mice with ADAM8 inactivated
title_fullStr	Elevated inflammatory gene expression in intervertebral disc tissues in mice with ADAM8 inactivated
title_full_unstemmed	Elevated inflammatory gene expression in intervertebral disc tissues in mice with ADAM8 inactivated
title_sort	elevated inflammatory gene expression in intervertebral disc tissues in mice with adam8 inactivated
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/29482a7dd36f42fc82304c841792897b
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Elevated inflammatory gene expression in intervertebral disc tissues in mice with ADAM8 inactivated

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