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Cyclic Strain Alters the Expression and Release of Angiogenic Factors by Human Tendon Cells
Authors:Rouhollah Mousavizadeh  Shahram Khosravi  Hayedeh Behzad  Robert G. McCormack  Vincent Duronio  Alex Scott
Affiliation:1. Department of Medicine, University of British Columbia, Vancouver, Canada.; 2. Department of Physical Therapy, University of British Columbia, Centre for Hip Health and Mobility, Vancouver Coastal Health Research Institute, Vancouver, Canada.; 3. Department of Dermatology and Skin Science, University of British Columbia, Vancouver, Canada.; 4. Department of Orthopedic Surgery, University of British Columbia, Vancouver, Canada.; University of Pittsburgh, United States of America,
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.
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