Tendon response to matrix unloading is determined by the patho-physiological niche

Stefania L. Wunderli, Ulrich Blache, Agnese Beretta Piccoli, Barbara Niederöst, Claude N. Holenstein, Fabian S. Passini, Unai Silván, Louise Bundgaard, Ulrich auf dem Keller, Jess G. Snedeker*

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

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Although the molecular mechanisms behind tendon disease remain obscure, aberrant stromal matrix turnover and tissue hypervascularity are known hallmarks of advanced tendinopathy. We harness a tendon explant model to unwind complex cross-talk between the stromal and vascular tissue compartments. We identify the hypervascular tendon niche as a state-switch that gates degenerative matrix remodeling within the tissue stroma. Here pathological conditions resembling hypervascular tendon disease provoke rapid cell-mediated tissue breakdown upon mechanical unloading, in contrast to unloaded tendons that remain functionally stable in physiological low-oxygen/-temperature niches. Analyses of the stromal tissue transcriptome and secretome reveal that a stromal niche with elevated tissue oxygenation and temperature drives a ROS mediated cellular stress response that leads to adoption of an immune-modulatory phenotype within the degrading stromal tissue. Degradomic analysis further reveals a surprisingly rich set of active matrix proteases behind the progressive loss of tissue mechanics. We conclude that the tendon stromal compartment responds to aberrant mechanical unloading in a manner that is highly dependent on the vascular niche, with ROS gating a complex proteolytic breakdown of the functional collagen backbone.
Original languageEnglish
JournalMatrix Biology
Pages (from-to)11-26
Number of pages16
Publication statusPublished - 2020


  • Tendon
  • Explant
  • Rective oxygen species (ROS)
  • Proteases
  • Tissue model


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