title: Hypoxia and PDGF have a synergistic effect that increases the expression of the angiogenetic peptide vascular endothelial growth factor in Achilles tendon fibroblasts.
abstract: BACKGROUND
  Angiogenesis, the formation of new blood vessels from pre-existing vessels, is an essential step in the process of tendon healing and tendon graft remodelling, e.g. after anterior cruciate ligament reconstruction. To address the question of whether platelet-derived growth factor (PDGF) could influence vascular endothelial growth factor (VEGF) expression in tenocytes, we challenged primary cultures of rat tenocytes with different stimulators (hypoxia, PDGF) and measured their VEGF secretion.
  
  
  METHODS
  To measure the VEGF secretion and the effect of PDGF, we used cell culture and stimulation of rat tenocytes (2-5 days old), immunohistochemistry as well as enzyme-linked immunosorbent assay (ELISA).
  
  
  RESULTS
  Tenocytes cultivated under normal oxygen pressure released measurable amounts of VEGF into their culture supernatants. Stimulation with PDGF, a cytokine that activates mitogen-activated protein kinases, raised VEGF secretion 2-fold. Hypoxic conditions alone (5% O(2)) raised VEGF secretion only 2-fold. However, the combination of cytokines and hypoxia increased VEGF production 5-fold, apparently a synergistic effect.
  
  
  CONCLUSIONS
  These data are useful to further our understanding of angiogenesis in tendon healing and tendon graft remodelling after ACL reconstruction.
authors.affiliation: Department of Orthopaedic Surgery, Christian Albrechts University, Michaelisstr. 1, 24105 Kiel, Germany. wolfpetersen@hotmail.com
authors.forename: Wolf
authors.initials: W
authors.lastname: Petersen
authors.forename: Thomas
authors.initials: T
authors.lastname: Pufe
authors.forename: Thore
authors.initials: T
authors.lastname: Zantop
authors.forename: Bernhard
authors.initials: B
authors.lastname: Tillmann
authors.forename: Rolf
authors.initials: R
authors.lastname: Mentlein
mesh_terms: D000125:Achilles Tendon / Q000166:cytology*; D000818:Animals; D015687:Cell Hypoxia / Q000502:physiology; D002478:Cells, Cultured; D005347:Fibroblasts / Q000378:metabolism*; D007150:Immunohistochemistry; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D051381:Rats; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*; D014945:Wound Healing / Q000502:physiology
chemical_list: D010982:Platelet-Derived Growth Factor; D042461:Vascular Endothelial Growth Factor A