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Release of tensile strain on engineered human tendon tissue disturbs cell adhesions, changes matrix architecture, and induces an inflammatory phenotype

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Authors:
  • Bayer, Monika L ;
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    Systems Biology Research, Department of Biomedical Sciences, Faculty of Health and Medical Sciences, Københavns Universitet
  • Schjerling, Peter ;
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    Department of Clinical Medicine, Faculty of Health and Medical Sciences, Københavns Universitet
  • Herchenhan, Andreas ;
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    Systems Biology Research, Department of Biomedical Sciences, Faculty of Health and Medical Sciences, Københavns Universitet
  • Zeltz, Cedric ;
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    Department of Biomedicine, University of Bergen, Bergen, Norway.
  • Heinemeier, Katja Maria ;
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    Systems Biology Research, Department of Biomedical Sciences, Faculty of Health and Medical Sciences, Københavns Universitet
  • Christensen, Lise ;
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    Section of Diagnostic Sciences, Department of Clinical Medicine, Faculty of Health and Medical Sciences, Københavns Universitet
  • Krogsgaard, Michael ;
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    Department of Clinical Medicine, Department of Clinical Medicine, Faculty of Health and Medical Sciences, Københavns Universitet
  • Gullberg, Donald ;
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    Department of Biomedicine, University of Bergen, Bergen, Norway.
  • Kjaer, Michael
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    Department of Clinical Medicine, Department of Clinical Medicine, Faculty of Health and Medical Sciences, Københavns Universitet
DOI:
10.1371/journal.pone.0086078
Abstract:
Mechanical loading of tendon cells results in an upregulation of mechanotransduction signaling pathways, cell-matrix adhesion and collagen synthesis, but whether unloading removes these responses is unclear. We investigated the response to tension release, with regard to matrix proteins, pro-inflammatory mediators and tendon phenotypic specific molecules, in an in vitro model where tendon-like tissue was engineered from human tendon cells. Tissue sampling was performed 1, 2, 4 and 6 days after surgical de-tensioning of the tendon construct. When tensile stimulus was removed, integrin type collagen receptors showed a contrasting response with a clear drop in integrin subunit α11 mRNA and protein expression, and an increase in α2 integrin mRNA and protein levels. Further, specific markers for tendon cell differentiation declined and normal tendon architecture was disturbed, whereas pro-inflammatory molecules were upregulated. Stimulation with the cytokine TGF-β1 had distinct effects on some tendon-related genes in both tensioned and de-tensioned tissue. These findings indicate an important role of mechanical loading for cellular and matrix responses in tendon, including that loss of tension leads to a decrease in phenotypical markers for tendon, while expression of pro-inflammatory mediators is induced.
Type:
Journal article
Language:
English
Published in:
Plos One, 2014, Vol 9, Issue 1, p. 1-16
Keywords:
Adolescent; Adult; Biological Markers; Cell Adhesion; Cellular Microenvironment; Collagen; Extracellular Matrix; Gene Expression Regulation; Humans; Inflammation; Inflammation Mediators; Integrins; Phenotype; Protein Subunits; RNA, Messenger; Stress, Mechanical; Tendons; Tensile Strength; Time Factors; Tissue Culture Techniques; Tissue Engineering; Tissue Scaffolds; Transforming Growth Factor beta1; Young Adult; Journal Article; Research Support, Non-U.S. Gov't
Main Research Area:
Medical science
Publication Status:
Published
Review type:
Peer Review
Submission year:
2014
Scientific Level:
Scientific
ID:
259717972

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