Expression of VEGF121 and VEGF165 in hypertrophic chondrocytes of the human growth plate and epiphyseal cartilage.

Abstract

Vascular endothelial growth factor (VEGF) plays an important role during endochondral bone formation in hypertrophic cartilage remodelling. We examined VEGF and VEGF receptor expression in tibiae from fetuses, newborns and children immunohistochemically. Expression of mRNA for the different VEGF splice forms and for VEGF receptors KDR and FLT-1 was analysed by reverse transcription-polymerase chain reaction (RT-PCR). VEGF could be immunolocalized intracellularly in the hypertrophic chondrocytes of the growth plate and in the chondrocytes around cartilage canals of the epiphysis, respectively. The resting zone and the proliferative zone of the growth plate were VEGF-negative. In cartilage samples of all growth plates analysed, VEGF121 and VEGF165 were identified as the only VEGF splice forms expressed. RT-PCR for VEGF mRNA of normal hyaline cartilage was negative. At vessels growing into the hypertrophic cartilage FLT-1 (VEGFR-1) and KDR (VGEFR-2) could be visualized. Reverse transcription-polymerase chain reaction (RT-PCR) substantiated the results regarding FLT-1 and KDR expression. The results of our study suggest that the splice forms VEGF121 and VEGF165 and the receptors KDR and FLT-1 of the known angiogenetic peptide VEGF play a role in process of endochondral ossification.