Inhibition of ERK 1/2 kinases prevents tendon matrix breakdown
OPEN ACCESS
Loading...
Author / Producer
Date
2021-03-25
Publication Type
Journal Article
ETH Bibliography
yes
Citations
Altmetric
OPEN ACCESS
Data
Rights / License
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.
Permanent link
Publication status
published
External links
Editor
Book title
Journal / series
Volume
11 (1)
Pages / Article No.
6838
Publisher
Springer
Event
Edition / version
Methods
Software
Geographic location
Date collected
Date created
Subject
Biochemistry; Cell biology; Cell signalling; Kinases; Proteases; Proteolysis
Organisational unit
03822 - Snedeker, Jess G. / Snedeker, Jess G.
Notes
Funding
Related publications and datasets
Is part of: https://doi.org/10.3929/ethz-b-000540613