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

Authors

  • Wolf Petersen,

    Corresponding author
    1. Department of Trauma, Hand, and Reconstructive Surgery, Westfaelische Wilhelms University, 48149 Muenster, Germany
    Current affiliation:
    1. Department of Trauma, Hand, and Reconstructive Surgery, University of Muenster, Waldeyerstrasse 1, Muenster D-48149, Germany
    • Department of Trauma, Hand, and Reconstructive Surgery, University of Muenster, Waldeyerstrasse 1, Muenster D-48149, Germany. Tel.: +49-251-83-56301/431-597-2444; fax: +49-251-83-56318/431-597-2509
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  • Deike Varoga,

    1. Department of Orthopaedic Surgery, Christian-Albrechts-University, 24 105 Kiel, Germany
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  • Thore Zantop,

    1. Department of Orthopaedic Surgery, Christian-Albrechts-University, 24 105 Kiel, Germany
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  • Joachim Hassenpflug,

    1. Department of Orthopaedic Surgery, Christian-Albrechts-University, 24 105 Kiel, Germany
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  • Rolf Mentlein,

    1. Department of Anatomy, Christian-Albrechts-University, 24 098 Kiel, Germany
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  • Thomas Pufe

    1. Department of Anatomy, Christian-Albrechts-University, 24 098 Kiel, Germany
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  • The current study was supported by a grant from the „Deutsche Forschungsgemeinschaft” (Pe 873/2-1).

Abstract

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-1α. These results demonstrate that mechanical factors are involved in the regulation of VEGF expression in tendon tissue. © 2003 Orthopaedic Research Society. Published by Elsevier Ltd. All rights reserved.

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