Cyclic strain alters the expression and release of angiogenic factors by human tendon cells

PLoS One. 2014 May 13;9(5):e97356. doi: 10.1371/journal.pone.0097356. eCollection 2014.

Abstract

Angiogenesis is associated with the tissue changes underlying chronic overuse tendinopathy. We hypothesized that repetitive, cyclic loading of human tendon cells would lead to increased expression and activity of angiogenic factors. We subjected isolated human tendon cells to overuse tensile loading using an in vitro model (1 Hz, 10% equibiaxial strain). We found that mechanically stimulated human tendon cells released factors that promoted in vitro proliferation and tube formation by human umbilical vein endothelial cells (HUVEC). In response to cyclic strain, there was a transient increase in the expression of several angiogenic genes including ANGPTL4, FGF-2, COX-2, SPHK1, TGF-alpha, VEGF-A and VEGF-C, with no change in anti-angiogenic genes (BAI1, SERPINF1, THBS1 and 2, TIMP1-3). Cyclic strain also resulted in the extracellular release of ANGPTL4 protein by tendon cells. Our study is the first report demonstrating the induction of ANGPTL4 mRNA and release of ANGPTL4 protein in response to cyclic strain. Tenocytes may contribute to the upregulation of angiogenesis during the development of overuse tendinopathy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Angiogenesis Inducing Agents / metabolism*
  • Angiopoietin-like 4 Protein
  • Angiopoietins / metabolism
  • Biomechanical Phenomena
  • Blotting, Western
  • Cumulative Trauma Disorders / metabolism
  • Cumulative Trauma Disorders / physiopathology*
  • Cyclooxygenase 2 / metabolism
  • DNA Primers / genetics
  • Enzyme-Linked Immunosorbent Assay
  • Fibroblast Growth Factor 2 / metabolism
  • Flow Cytometry
  • Gene Expression Profiling
  • Gene Expression Regulation / physiology*
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • In Vitro Techniques
  • Phosphotransferases (Alcohol Group Acceptor) / metabolism
  • Physical Stimulation
  • Stress, Physiological / physiology*
  • Tendons / cytology
  • Tendons / metabolism*
  • Transforming Growth Factor alpha / metabolism
  • Vascular Endothelial Growth Factor A / metabolism
  • Vascular Endothelial Growth Factor C / metabolism

Substances

  • ANGPTL4 protein, human
  • Angiogenesis Inducing Agents
  • Angiopoietin-like 4 Protein
  • Angiopoietins
  • DNA Primers
  • Transforming Growth Factor alpha
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factor C
  • Fibroblast Growth Factor 2
  • Cyclooxygenase 2
  • PTGS2 protein, human
  • Phosphotransferases (Alcohol Group Acceptor)
  • sphingosine kinase