27 research outputs found
No donor age effect of human serum on collagen synthesis signaling and cell proliferation of human tendon fibroblasts
GH/IGF-I axis and matrix adaptation of the musculotendinous tissue to exercise in humans
Release of Tensile Strain on Engineered Human Tendon Tissue Disturbs Cell Adhesions, Changes Matrix Architecture, and Induces an Inflammatory Phenotype
<div><p>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 <i>in vitro</i> 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 α<sub>11</sub> mRNA and protein expression, and an increase in α<sub>2</sub> 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.</p></div
Summary of findings after de-tensioning of 3D tendon-constructs and TGF-β1 supplementation.
<p>The 3D tendon-construct under static tension without TGF-β1 is set as baseline, all other conditions are shown relative to the tensioned 3D tendon-construct (n = 5). A) Analysis of genes encoding for different matrix proteins: Collagen type I (COL1A1), collagen type III (COL3A1), collagen type XII (COL12A1) collagen type XIV (COL14A1) and fibronectin. B) Analysis of tendon phenotypic markers and tendon-related genes: tenomodulin (TNMD), scleraxis (SCX), Mohawk homeobox (MKX), fibromodulin (FBMD), decorin and GAPDH. Data presented on a logarithmic y scale as geometric means ± SEM with 3D tendon construct as baseline (n = 5). Significant 2-way ANOVA (tension*TGF-β1) main effects written above the graphs. For FBMD, * indicates significant effect of TGF-β1 for the individual groups in the post hoc analysis.</p
Overview over the effect of de-tensioning and TGF-β1 supplementation on mRNA expression of tendon matrix genes and growth factors.
<p>Left panel (A, D, G, J): Effect of de-tensioning, mid panel (B, E, H, K): Effect of TGF-β1 on tensioned 3D tendon-constructs, right panel (C, F, I, L): Effect of TGF-β1 on de-tensioned 3D tendon-constructs. The data are presented on a logarithmic y scale as geometric means ± SD (n = 3) where Tension Day 1 is baseline. Significant 2-way RM ANOVA (tension*time) or (TGF-β1*time) main effects written above the graphs. Open triangles: 3D tendon-construct under tension, without TGF-β1 supplementation; open circles: 3D tendon-construct de-tensioned, without TGF-β1 supplementation; filled triangles: 3D tendon-construct under tension, with TGF-β1 supplementation; filled circles: 3D tendon-construct de-tensioned, with TGF-β1 supplementation.</p
Summary of mRNA expression of tendon-related genes as a response to changes in the spatial/mechanical environment and TGF-β1 supplementation.
<p>Summary of <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0086078#pone-0086078-g002" target="_blank">figure 2</a> and <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0086078#pone-0086078-g003" target="_blank">3:</a> The effect of the intervention is compared to the gene expression of the respective target cultured for six days under static tension, the arrows (↑↓) indicate significant changes relative to the tensioned samples, or no statistical change (↔). Arrows in parenthesis indicate a tendency (p< 0.1). Tenomodulin (TNMD); Scleraxis (SCX); Mohawk homeobox (MKX); Collagen type I (COL1A1); collagen type III (COL3A1); collagen type XII (COL12A1); collagen type XIV (COL14A1); Fibronectin (FN); Decorin (DCN); Fibromodulin (FBMD); Transforming growth factor-β1 (TGFB1); Connective tissue growth factor (CCN2); Glyceraldehyde 3-phosphate dehydrogenase (GAPDH).</p
Comparison between 2D monolayer and 3D tendon-constructs under static tension.
<p>The 3D tendon-construct is set as baseline, and mRNA expression of tendon cells grown on 2D monolayer is shown relative to the 3D tendon construct. Significant changes are indicated by *. Data presented on a logarithmic y scale baseline as geometric means ± SEM with 3D tendon-construct as baseline (n = 5).</p
Safety and efficacy of low-molecular-weight heparin in pregnant women at increased risk of venous thromboembolism: A prospective stratified multicentre trial
Overview over the effect of de-tensioning on protein expression of different integrin subunits.
<p>A) Effect of de-tensioning on integrin sub-unit α5, B) Effect of de-tensioning on integrin sub-unit α11, C) Effect of de-tensioning on integrin sub-unit β1. The data are presented on a logarithmic y scale as geometric means ± SD (n = 3) where Tension Day 1 is baseline. Significant 2-way RM ANOVA (tension*time) main effects written above the graphs. Open triangles: 3D tendon-construct under tension, without TGF-β1 supplementation; open circles: 3D tendon-construct de-tensioned, without TGF-β1 supplementation. Below the graphs, representative western blots are shown (+/- tension).</p