Cyclic strain alters the expression and release of angiogenic factors by human tendon cells.
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.
Department of Medicine, University of British Columbia, Vancouver, Canada; Department of Physical Therapy, University of British Columbia, Centre for Hip Health and Mobility, Vancouver Coastal Health Research Institute, Vancouver, Canada.
Rouhollah
R
Mousavizadeh
Department of Dermatology and Skin Science, University of British Columbia, Vancouver, Canada.
Shahram
S
Khosravi
Department of Physical Therapy, University of British Columbia, Centre for Hip Health and Mobility, Vancouver Coastal Health Research Institute, Vancouver, Canada.
Hayedeh
H
Behzad
Department of Orthopedic Surgery, University of British Columbia, Vancouver, Canada.
Robert G
RG
McCormack
Department of Medicine, University of British Columbia, Vancouver, Canada.
Vincent
V
Duronio
Department of Physical Therapy, University of British Columbia, Centre for Hip Health and Mobility, Vancouver Coastal Health Research Institute, Vancouver, Canada.
Alex
A
Scott
D000704:Analysis of Variance; D043925:Angiogenesis Inducing Agents / Q000378:metabolism*; D000075803:Angiopoietin-Like Protein 4; D042682:Angiopoietins / Q000378:metabolism; D001696:Biomechanical Phenomena; D015153:Blotting, Western; D012090:Cumulative Trauma Disorders / Q000378:metabolism / Q000503:physiopathology*; D051546:Cyclooxygenase 2 / Q000378:metabolism; D017931:DNA Primers / Q000235:genetics; D004797:Enzyme-Linked Immunosorbent Assay; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000502:physiology*; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D066298:In Vitro Techniques; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000378:metabolism; D010812:Physical Stimulation; D013312:Stress, Physiological / Q000502:physiology*; D013710:Tendons / Q000166:cytology / Q000378:metabolism*; D016211:Transforming Growth Factor alpha / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D042582:Vascular Endothelial Growth Factor C / Q000378:metabolism; D000099157:Sphingosine Kinase
D043925:Angiogenesis Inducing Agents; D000075803:Angiopoietin-Like Protein 4; D042682:Angiopoietins; D051546:Cyclooxygenase 2; D017931:DNA Primers; D016222:Fibroblast Growth Factor 2; D017853:Phosphotransferases (Alcohol Group Acceptor); D016211:Transforming Growth Factor alpha; D042461:Vascular Endothelial Growth Factor A; D042582:Vascular Endothelial Growth Factor C; D000099157:Sphingosine Kinase; C474772:ANGPTL4 protein, human; C496540:PTGS2 protein, human