Angiogenesis is a crucial event in endochondral ossification, Chemoattracta
nts and mitogens for endothelial cells (such as basic fibroblast growth fac
tor [bFGF] and transforming growth factor beta [TGF-beta]), which act as lo
cal regulators of the process, are synthesized by chondrocytes under severa
l stimuli and in relation to the differentiation stage of the cartilage. Va
scular endothelial growth factor (VEGF) is a 44-kDa protein well known as a
potent angiogenic molecule owing to its mitogenic and permeability-causing
properties. In this work, VEGF was located by immunohistochemistry in grow
th plate cartilage of human fetuses (20-22 weeks old) and its expression wa
s demonstrated by reverse-transcription polymerase chain reaction (RT-PCR),
Primary culture of human fetal epiphyseal chondrocytes (HFEC) maintained V
EGF expression at protein and messenger RNA (mRNA) levels and this expressi
on was stimulated by cartilage-promoting growth factors incorporated into t
he culture media (rFGF-b, rTGF-beta 1, and insulin-like growth factor [rIGF
-I] at 50 ng/ml), The conditioned medium (CM) of HFEC stimulated the prolif
eration of endothelial cells, and this was partially blocked by anti-VEGF a
ntibody. These studies showed VEGF production by chondrocytes of the epiphy
seal growth cartilage and suggested a role of this factor in cartilage phys
iology and the angiogenic process.