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

PLoS One. 2014 Jan 21;9(1):e86078. doi: 10.1371/journal.pone.0086078. eCollection 2014.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Biomarkers / metabolism
  • Cell Adhesion
  • Cellular Microenvironment / drug effects
  • Collagen / genetics
  • Collagen / metabolism
  • Extracellular Matrix / chemistry*
  • Extracellular Matrix / drug effects
  • Extracellular Matrix / genetics
  • Gene Expression Regulation / drug effects
  • Humans
  • Inflammation / pathology*
  • Inflammation Mediators / metabolism
  • Integrins / metabolism
  • Phenotype
  • Protein Subunits / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Stress, Mechanical
  • Tendons / cytology*
  • Tendons / drug effects
  • Tendons / physiology*
  • Tendons / ultrastructure
  • Tensile Strength*
  • Time Factors
  • Tissue Culture Techniques
  • Tissue Engineering / methods*
  • Tissue Scaffolds
  • Transforming Growth Factor beta1 / pharmacology
  • Young Adult

Substances

  • Biomarkers
  • Inflammation Mediators
  • Integrins
  • Protein Subunits
  • RNA, Messenger
  • Transforming Growth Factor beta1
  • Collagen