Cyclic strain influences the expression of the vascular endothelial growth factor (VEGF) and the hypoxia inducible factor 1 alpha (HIF-1alpha) in tendon fibroblasts

J Orthop Res. 2004 Jul;22(4):847-53. doi: 10.1016/j.orthres.2003.11.009.


Neovascularization is involved in beneficial and detrimental processes of tendon pathology. We investigated the influence of repetitive motion on the expression of the most important angiogenic factor, the vascular endothelial growth factor (VEGF) in the 3T3 NIH fibroblast cell line and in cultures of rat Achilles tendon fibroblasts. Monolayers of subconfluently grown cells were stretched in rectangular silicone dishes with cyclic uniaxial movement. Strain was applied over 24 h varying the frequency (0.5-1 Hz). Fibroblasts (3T3 fibroblasts and rat Achilles tendon cultures) cultivated without the application of cyclic strain released measurable VEGF amounts into their culture supernatants. Cyclic stretching of the cells with a frequency of 1 Hz resulted in an increased expression of VEGF. A low frequency (0.5 Hz) reduced VEGF expression to control levels. RT PCR revealed VEGF 121 and VEGF 165 as the only splice forms that were induced by cyclic stretching. Western blot experiments could further show that cyclic stretching induced activation of the transcription factor HIF-1alpha. These results demonstrate that mechanical factors are involved in the regulation of VEGF expression in tendon tissue.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3 Cells
  • Achilles Tendon / cytology
  • Achilles Tendon / metabolism*
  • Achilles Tendon / physiology
  • Alternative Splicing
  • Animals
  • Animals, Newborn
  • Blotting, Western
  • Culture Media, Conditioned / chemistry
  • Fibroblasts / cytology
  • Fibroblasts / metabolism*
  • Fibroblasts / physiology
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Immunohistochemistry
  • Mice
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Rats
  • Reverse Transcriptase Polymerase Chain Reaction
  • Stress, Mechanical
  • Transcription Factors / analysis
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Transcription, Genetic*
  • Vascular Endothelial Growth Factor A / analysis
  • Vascular Endothelial Growth Factor A / genetics
  • Vascular Endothelial Growth Factor A / metabolism*


  • Culture Media, Conditioned
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • RNA, Messenger
  • Transcription Factors
  • Vascular Endothelial Growth Factor A