Inhibition of ERK 1/2 kinases prevents tendon matrix breakdown

Abstract Tendon extracellular matrix (ECM) mechanical unloading results in tissue degradation and breakdown, with niche-dependent cellular stress directing proteolytic degradation of tendon. Here, we show that the extracellular-signal regulated kinase (ERK) pathway is central in tendon degradation o...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Ulrich Blache, Stefania L. Wunderli, Amro A. Hussien, Tino Stauber, Gabriel Flückiger, Maja Bollhalder, Barbara Niederöst, Sandro F. Fucentese, Jess G. Snedeker
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/5855c215acdf4349bfb11315c1a27b02
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:5855c215acdf4349bfb11315c1a27b02
record_format	dspace
spelling	oai:doaj.org-article:5855c215acdf4349bfb11315c1a27b022021-12-02T17:04:07ZInhibition of ERK 1/2 kinases prevents tendon matrix breakdown10.1038/s41598-021-85331-12045-2322https://doaj.org/article/5855c215acdf4349bfb11315c1a27b022021-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-85331-1https://doaj.org/toc/2045-2322Abstract Tendon extracellular matrix (ECM) mechanical unloading results in tissue degradation and breakdown, with niche-dependent cellular stress directing proteolytic degradation of tendon. Here, we show that the extracellular-signal regulated kinase (ERK) pathway is central in tendon degradation of load-deprived tissue explants. We show that ERK 1/2 are highly phosphorylated in mechanically unloaded tendon fascicles in a vascular niche-dependent manner. Pharmacological inhibition of ERK 1/2 abolishes the induction of ECM catabolic gene expression (MMPs) and fully prevents loss of mechanical properties. Moreover, ERK 1/2 inhibition in unloaded tendon fascicles suppresses features of pathological tissue remodeling such as collagen type 3 matrix switch and the induction of the pro-fibrotic cytokine interleukin 11. This work demonstrates ERK signaling as a central checkpoint to trigger tendon matrix degradation and remodeling using load-deprived tissue explants.Ulrich BlacheStefania L. WunderliAmro A. HussienTino StauberGabriel FlückigerMaja BollhalderBarbara NiederöstSandro F. FucenteseJess G. SnedekerNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-9 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Ulrich Blache Stefania L. Wunderli Amro A. Hussien Tino Stauber Gabriel Flückiger Maja Bollhalder Barbara Niederöst Sandro F. Fucentese Jess G. Snedeker Inhibition of ERK 1/2 kinases prevents tendon matrix breakdown
description	Abstract Tendon extracellular matrix (ECM) mechanical unloading results in tissue degradation and breakdown, with niche-dependent cellular stress directing proteolytic degradation of tendon. Here, we show that the extracellular-signal regulated kinase (ERK) pathway is central in tendon degradation of load-deprived tissue explants. We show that ERK 1/2 are highly phosphorylated in mechanically unloaded tendon fascicles in a vascular niche-dependent manner. Pharmacological inhibition of ERK 1/2 abolishes the induction of ECM catabolic gene expression (MMPs) and fully prevents loss of mechanical properties. Moreover, ERK 1/2 inhibition in unloaded tendon fascicles suppresses features of pathological tissue remodeling such as collagen type 3 matrix switch and the induction of the pro-fibrotic cytokine interleukin 11. This work demonstrates ERK signaling as a central checkpoint to trigger tendon matrix degradation and remodeling using load-deprived tissue explants.
format	article
author	Ulrich Blache Stefania L. Wunderli Amro A. Hussien Tino Stauber Gabriel Flückiger Maja Bollhalder Barbara Niederöst Sandro F. Fucentese Jess G. Snedeker
author_facet	Ulrich Blache Stefania L. Wunderli Amro A. Hussien Tino Stauber Gabriel Flückiger Maja Bollhalder Barbara Niederöst Sandro F. Fucentese Jess G. Snedeker
author_sort	Ulrich Blache
title	Inhibition of ERK 1/2 kinases prevents tendon matrix breakdown
title_short	Inhibition of ERK 1/2 kinases prevents tendon matrix breakdown
title_full	Inhibition of ERK 1/2 kinases prevents tendon matrix breakdown
title_fullStr	Inhibition of ERK 1/2 kinases prevents tendon matrix breakdown
title_full_unstemmed	Inhibition of ERK 1/2 kinases prevents tendon matrix breakdown
title_sort	inhibition of erk 1/2 kinases prevents tendon matrix breakdown
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/5855c215acdf4349bfb11315c1a27b02
work_keys_str_mv	AT ulrichblache inhibitionoferk12kinasespreventstendonmatrixbreakdown AT stefanialwunderli inhibitionoferk12kinasespreventstendonmatrixbreakdown AT amroahussien inhibitionoferk12kinasespreventstendonmatrixbreakdown AT tinostauber inhibitionoferk12kinasespreventstendonmatrixbreakdown AT gabrielfluckiger inhibitionoferk12kinasespreventstendonmatrixbreakdown AT majabollhalder inhibitionoferk12kinasespreventstendonmatrixbreakdown AT barbaraniederost inhibitionoferk12kinasespreventstendonmatrixbreakdown AT sandroffucentese inhibitionoferk12kinasespreventstendonmatrixbreakdown AT jessgsnedeker inhibitionoferk12kinasespreventstendonmatrixbreakdown
_version_	1718381849000017920

Inhibition of ERK 1/2 kinases prevents tendon matrix breakdown

Ejemplares similares