TY - JOUR

T1 - Release of tensile strain on engineered human tendon tissue disturbs cell adhesions, changes matrix architecture, and induces an inflammatory phenotype

AU - Bayer, Monika L

AU - Schjerling, Peter

AU - Herchenhan, Andreas

AU - Zeltz, Cedric

AU - Heinemeier, Katja Maria

AU - Christensen, Lise

AU - Krogsgaard, Michael

AU - Gullberg, Donald

AU - Kjaer, Michael

PY - 2014

Y1 - 2014

N2 - 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.

AB - 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.

KW - Adolescent

KW - Adult

KW - Biological Markers

KW - Cell Adhesion

KW - Cellular Microenvironment

KW - Collagen

KW - Extracellular Matrix

KW - Gene Expression Regulation

KW - Humans

KW - Inflammation

KW - Inflammation Mediators

KW - Integrins

KW - Phenotype

KW - Protein Subunits

KW - RNA, Messenger

KW - Stress, Mechanical

KW - Tendons

KW - Tensile Strength

KW - Time Factors

KW - Tissue Culture Techniques

KW - Tissue Engineering

KW - Tissue Scaffolds

KW - Transforming Growth Factor beta1

KW - Young Adult

U2 - 10.1371/journal.pone.0086078

DO - 10.1371/journal.pone.0086078

M3 - Journal article

C2 - 24465881

VL - 9

SP - 1

EP - 16

JO - PLoS ONE

JF - PLoS ONE

SN - 1932-6203

IS - 1

M1 - e86078

ER -