Angiogenesis is essential for the replacement of cartilage by bone during growth and repair. In order to
obtain a better understanding of the mechanisms regulating vascular invasion at sites of endochondral
ossification we have investigated the expression of the endothelial cell-specific mitogen, vascular endothelial
growth factor (VEGF), by chondrocytes in human neonatal growth plates. VEGF was absent from
chondrocytes in the resting zone and only weakly expressed by occasional chondrocytes in the proliferating
region. In the hypertrophic zone the number of chondrocytes stained and the intensity of staining for VEGF
increased with chondrocyte hypertrophy, maximum expression of VEGF being observed in chondrocytes in
the lower hypertrophic and mineralised regions of the cartilage. These observations provide the first
demonstration of the presence of VEGF in situ in developing human bone and are consistent with in vitro
observations demonstrating the upregulation of proangiogenic growth factor production with increasing
chondrocyte hypertrophy. The presence of numerous small blood vessels and vascular structures in the
subchondral region where VEGF expression was maximal indicates that VEGF produced by hypertrophic
chondrocytes may play a key role in the regulation of vascular invasion of the growth plate.