Activation of nuclear factor-kappa B by TNF promotes nucleus pulposus mineralization through inhibition of ANKH and ENPP1

Abstract Spontaneous mineralization of the nucleus pulposus (NP) has been observed in cases of intervertebral disc degeneration (IDD). Inflammatory cytokines have been implicated in mineralization of multiple tissues through their modulation of expression of factors that enable or inhibit mineraliza...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Agata K. Krzyzanowska, Robert J. Frawley, Sheela Damle, Tony Chen, Miguel Otero, Matthew E. Cunningham
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/d774118d3da34834890dc5881ee8e16d
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:d774118d3da34834890dc5881ee8e16d
record_format	dspace
spelling	oai:doaj.org-article:d774118d3da34834890dc5881ee8e16d2021-12-02T14:27:45ZActivation of nuclear factor-kappa B by TNF promotes nucleus pulposus mineralization through inhibition of ANKH and ENPP110.1038/s41598-021-87665-22045-2322https://doaj.org/article/d774118d3da34834890dc5881ee8e16d2021-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-87665-2https://doaj.org/toc/2045-2322Abstract Spontaneous mineralization of the nucleus pulposus (NP) has been observed in cases of intervertebral disc degeneration (IDD). Inflammatory cytokines have been implicated in mineralization of multiple tissues through their modulation of expression of factors that enable or inhibit mineralization, including TNAP, ANKH or ENPP1. This study examines the underlying factors leading to NP mineralization, focusing on the contribution of the inflammatory cytokine, TNF, to this pathologic event. We show that human and bovine primary NP cells express high levels of ANKH and ENPP1, and low or undetectable levels of TNAP. Bovine NPs transduced to express TNAP were capable of matrix mineralization, which was further enhanced by ANKH knockdown. TNF treatment or overexpression promoted a greater increase in mineralization of TNAP-expressing cells by downregulating the expression of ANKH and ENPP1 via NF-κB activation. The increased mineralization was accompanied by phenotypic changes that resemble chondrocyte hypertrophy, including increased RUNX2 and COL10A1 mRNA; mirroring the cellular alterations typical of samples from IDD patients. Disc organ explants injected with TNAP/TNF- or TNAP/shANKH-overexpressing cells showed increased mineral content inside the NP. Together, our results confirm interactions between TNF and downstream regulators of matrix mineralization in NP cells, providing evidence to suggest their participation in NP calcification during IDD.Agata K. KrzyzanowskaRobert J. FrawleySheela DamleTony ChenMiguel OteroMatthew E. CunninghamNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-15 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Agata K. Krzyzanowska Robert J. Frawley Sheela Damle Tony Chen Miguel Otero Matthew E. Cunningham Activation of nuclear factor-kappa B by TNF promotes nucleus pulposus mineralization through inhibition of ANKH and ENPP1
description	Abstract Spontaneous mineralization of the nucleus pulposus (NP) has been observed in cases of intervertebral disc degeneration (IDD). Inflammatory cytokines have been implicated in mineralization of multiple tissues through their modulation of expression of factors that enable or inhibit mineralization, including TNAP, ANKH or ENPP1. This study examines the underlying factors leading to NP mineralization, focusing on the contribution of the inflammatory cytokine, TNF, to this pathologic event. We show that human and bovine primary NP cells express high levels of ANKH and ENPP1, and low or undetectable levels of TNAP. Bovine NPs transduced to express TNAP were capable of matrix mineralization, which was further enhanced by ANKH knockdown. TNF treatment or overexpression promoted a greater increase in mineralization of TNAP-expressing cells by downregulating the expression of ANKH and ENPP1 via NF-κB activation. The increased mineralization was accompanied by phenotypic changes that resemble chondrocyte hypertrophy, including increased RUNX2 and COL10A1 mRNA; mirroring the cellular alterations typical of samples from IDD patients. Disc organ explants injected with TNAP/TNF- or TNAP/shANKH-overexpressing cells showed increased mineral content inside the NP. Together, our results confirm interactions between TNF and downstream regulators of matrix mineralization in NP cells, providing evidence to suggest their participation in NP calcification during IDD.
format	article
author	Agata K. Krzyzanowska Robert J. Frawley Sheela Damle Tony Chen Miguel Otero Matthew E. Cunningham
author_facet	Agata K. Krzyzanowska Robert J. Frawley Sheela Damle Tony Chen Miguel Otero Matthew E. Cunningham
author_sort	Agata K. Krzyzanowska
title	Activation of nuclear factor-kappa B by TNF promotes nucleus pulposus mineralization through inhibition of ANKH and ENPP1
title_short	Activation of nuclear factor-kappa B by TNF promotes nucleus pulposus mineralization through inhibition of ANKH and ENPP1
title_full	Activation of nuclear factor-kappa B by TNF promotes nucleus pulposus mineralization through inhibition of ANKH and ENPP1
title_fullStr	Activation of nuclear factor-kappa B by TNF promotes nucleus pulposus mineralization through inhibition of ANKH and ENPP1
title_full_unstemmed	Activation of nuclear factor-kappa B by TNF promotes nucleus pulposus mineralization through inhibition of ANKH and ENPP1
title_sort	activation of nuclear factor-kappa b by tnf promotes nucleus pulposus mineralization through inhibition of ankh and enpp1
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/d774118d3da34834890dc5881ee8e16d
work_keys_str_mv	AT agatakkrzyzanowska activationofnuclearfactorkappabbytnfpromotesnucleuspulposusmineralizationthroughinhibitionofankhandenpp1 AT robertjfrawley activationofnuclearfactorkappabbytnfpromotesnucleuspulposusmineralizationthroughinhibitionofankhandenpp1 AT sheeladamle activationofnuclearfactorkappabbytnfpromotesnucleuspulposusmineralizationthroughinhibitionofankhandenpp1 AT tonychen activationofnuclearfactorkappabbytnfpromotesnucleuspulposusmineralizationthroughinhibitionofankhandenpp1 AT miguelotero activationofnuclearfactorkappabbytnfpromotesnucleuspulposusmineralizationthroughinhibitionofankhandenpp1 AT matthewecunningham activationofnuclearfactorkappabbytnfpromotesnucleuspulposusmineralizationthroughinhibitionofankhandenpp1
_version_	1718391280673751040

Activation of nuclear factor-kappa B by TNF promotes nucleus pulposus mineralization through inhibition of ANKH and ENPP1

Ejemplares similares