Reciprocal Actions of Platelet-Secreted TGF-??1 on the Production of VEGF and HGF by Human Tendon Cells

Abstract

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. 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. 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). The balance between TGF-beta1 and the pools of platelet-secreted molecules may have important therapeutic implications in the control of angiogenesis and fibrosis.