title: Reciprocal actions of platelet-secreted TGF-beta1 on the production of VEGF and HGF by human tendon cells.
abstract: BACKGROUND
  Autologous platelet-rich matrices can be an aid in surgery by promoting and accelerating tissue healing because of the release of growth factors including transforming growth factor (TGF)-beta1 and platelet-derived growth factor (PDGF) from platelet alpha-granules.
  
  
  METHODS
  PDGF and TGF-beta1 were quantified in supernatants collected from platelet-rich matrices prepared in vitro (n = 45 donors) and they correlated with the number of platelets and showed a constant ratio (p < 0.05). Tendon cells in culture were exposed to the supernatants (n = 4 donors) from either platelet-rich or platelet-poor matrices, differing in their content of platelet-secreted molecules. These treatments were modified by either neutralizing or adding PDGF or TGF-beta1. Effects were compared in terms of proliferation, procollagen I, vascular endothelial growth factor (VEGF), and hepatocyte growth factor (HGF) production.
  
  
  RESULTS
  PDGF was a partial contributor to cell proliferation, whereas exogenous TGF-beta1 acted as a negative modulator (p < 0.05). The production of type I collagen was similar regardless of differences in the concentration of TGF-beta1. Moreover, addition of exogenous TGF-beta1 promoted a significant increase in collagen synthesis only in the absence of other platelet-released substances (p < 0.05). Exogenous TGF-beta1 increased the synthesis of VEGF and simultaneously abolished the production of HGF. Furthermore, antibody-mediated neutralization of TGF-beta1 induced a decrease in VEGF synthesis and concomitantly a substantial production of HGF (p < 0.05).
  
  
  CONCLUSIONS
  The balance between TGF-beta1 and the pools of platelet-secreted molecules may have important therapeutic implications in the control of angiogenesis and fibrosis.
authors.affiliation: Biotechnology Institute IMASD, Unidad de Cirugía Artroscópica Mikel Sanchez, Vitoria, Spain.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Anitua
authors.forename: Mikel
authors.initials: M
authors.lastname: Sanchez
authors.forename: Alan T
authors.initials: AT
authors.lastname: Nurden
authors.forename: Mar
authors.initials: M
authors.lastname: Zalduendo
authors.forename: Maria
authors.initials: M
authors.lastname: de la Fuente
authors.forename: Juan
authors.initials: J
authors.lastname: Azofra
authors.forename: Isabel
authors.initials: I
authors.lastname: Andia
mesh_terms: D000328:Adult; D000368:Aged; D001792:Blood Platelets / Q000378:metabolism*; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D024042:Collagen Type I / Q000378:metabolism; D017077:Culture Media, Conditioned; D005260:Female; D017228:Hepatocyte Growth Factor / Q000096:biosynthesis*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010976:Platelet Count; D010982:Platelet-Derived Growth Factor / Q000096:biosynthesis / Q000494:pharmacology; D011347:Procollagen / Q000378:metabolism; D013710:Tendons / Q000166:cytology / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism / Q000494:pharmacology*; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis*; D014945:Wound Healing / Q000502:physiology
chemical_list: D024042:Collagen Type I; D017077:Culture Media, Conditioned; D010982:Platelet-Derived Growth Factor; D011347:Procollagen; D053773:Transforming Growth Factor beta1; D042461:Vascular Endothelial Growth Factor A; D017228:Hepatocyte Growth Factor