Scientific Reports (Mar 2021)

Inhibition of ERK 1/2 kinases prevents tendon matrix breakdown

  • Ulrich Blache,
  • Stefania L. Wunderli,
  • Amro A. Hussien,
  • Tino Stauber,
  • Gabriel Flückiger,
  • Maja Bollhalder,
  • Barbara Niederöst,
  • Sandro F. Fucentese,
  • Jess G. Snedeker

DOI
https://doi.org/10.1038/s41598-021-85331-1
Journal volume & issue
Vol. 11, no. 1
pp. 1 – 9

Abstract

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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.