Hypoxia and PDGF have a synergistic effect that increases the expression of the angiogenetic peptide vascular endothelial growth factor in Achilles tendon fibroblasts.

Abstract

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. 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). 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. These data are useful to further our understanding of angiogenesis in tendon healing and tendon graft remodelling after ACL reconstruction.