Journal article · Ahead of Print article
Tendon response to matrix unloading is determined by the patho-physiological niche
Balgrist University Hospital1
Department of Biotechnology and Biomedicine, Technical University of Denmark2
DTU Proteomics Core, Section for Protein Science and Biotherapeutics, Department of Biotechnology and Biomedicine, Technical University of Denmark3
Protease Network Degradomics, Section for Protein Science and Biotherapeutics, Department of Biotechnology and Biomedicine, Technical University of Denmark4
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.
Language: | English |
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Year: | 2020 |
Pages: | 11-26 |
ISSN: | 15691802 and 0945053x |
Types: | Journal article and Ahead of Print article |
DOI: | 10.1016/j.matbio.2019.12.003 |
ORCIDs: | 0000-0001-8376-7052 , 0000-0002-1258-4002 , 0000-0003-0757-3621 , Bundgaard, Louise and auf dem Keller, Ulrich |