Inhibition of ERK 1/2 kinases prevents tendon matrix breakdown
dc.contributor.author
Blache, Ulrich
dc.contributor.author
Wunderli, Stefania L.
dc.contributor.author
Hussien, Amro A.
dc.contributor.author
Stauber, Tino
dc.contributor.author
Flückiger, Gabriel
dc.contributor.author
Bollhalder, Maja
dc.contributor.author
Niederöst, Barbara
dc.contributor.author
Fucentese, Sandro F.
dc.contributor.author
Snedeker, Jess Gerrit
dc.date.accessioned
2021-04-12T12:15:50Z
dc.date.available
2021-04-03T02:56:34Z
dc.date.available
2021-04-12T12:15:50Z
dc.date.issued
2021-03-25
dc.identifier.issn
2045-2322
dc.identifier.other
10.1038/s41598-021-85331-1
en_US
dc.identifier.uri
http://hdl.handle.net/20.500.11850/477382
dc.identifier.doi
10.3929/ethz-b-000477382
dc.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.
en_US
dc.format
application/pdf
en_US
dc.language.iso
en
en_US
dc.publisher
Springer
en_US
dc.rights.uri
http://creativecommons.org/licenses/by/4.0/
dc.subject
Biochemistry
en_US
dc.subject
Cell biology
en_US
dc.subject
Cell signalling
en_US
dc.subject
Kinases
en_US
dc.subject
Proteases
en_US
dc.subject
Proteolysis
en_US
dc.title
Inhibition of ERK 1/2 kinases prevents tendon matrix breakdown
en_US
dc.type
Journal Article
dc.rights.license
Creative Commons Attribution 4.0 International
ethz.journal.title
Scientific Reports
ethz.journal.volume
11
en_US
ethz.journal.issue
1
en_US
ethz.journal.abbreviated
Sci Rep
ethz.pages.start
6838
en_US
ethz.size
9 p.
en_US
ethz.version.deposit
publishedVersion
en_US
ethz.identifier.wos
ethz.identifier.scopus
ethz.publication.place
London
en_US
ethz.publication.status
published
en_US
ethz.leitzahl
ETH Zürich::00002 - ETH Zürich::00012 - Lehre und Forschung::00007 - Departemente::02070 - Dep. Gesundheitswiss. und Technologie / Dep. of Health Sciences and Technology::02518 - Institut für Biomechanik / Institute for Biomechanics::03822 - Snedeker, Jess G. / Snedeker, Jess G.
ethz.leitzahl.certified
ETH Zürich::00002 - ETH Zürich::00012 - Lehre und Forschung::00007 - Departemente::02070 - Dep. Gesundheitswiss. und Technologie / Dep. of Health Sciences and Technology::02518 - Institut für Biomechanik / Institute for Biomechanics::03822 - Snedeker, Jess G. / Snedeker, Jess G.
ethz.relation.isPartOf
10.3929/ethz-b-000540613
ethz.date.deposited
2021-04-03T02:56:39Z
ethz.source
SCOPUS
ethz.eth
yes
en_US
ethz.availability
Open access
en_US
ethz.rosetta.installDate
2021-04-12T12:16:01Z
ethz.rosetta.lastUpdated
2022-03-29T06:29:45Z
ethz.rosetta.versionExported
true
ethz.COinS
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