Differential effects of vascular endothelial growth factor on joint formation during limb development.

During skeletal development the proliferating chondrocytes choose between two fates: to differentiate into prejoint cells or undergo hypertrophy. Vascular endothelial growth factor (VEGF) participates in endochondral ossification, but it is unknown whether it has a role in joint development. We evaluated the VEGF effects on joints, implanting VEGF-beads in the presumptive limb joints of chick embryos. The wrist and elbow showed partial and complete fusions. Using the model of ectopic digits induced by transforming growth factor-beta (TGF-beta), VEGF inhibited joint formation when it was applied after TGF-beta. These data suggest differential effects of VEGF on different joints during development.