Expression of VEGF121 and VEGF165 in hypertrophic chondrocytes of the human growth plate and epiphyseal cartilage.
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.
Petersen
Wolf
W
wolfpetersen@hotmail.com
Tsokos
Michael
M
Pufe
Thomas
T
D000293:Adolescent; D017398:Alternative Splicing; D002356:Cartilage / Q000737:chemistry* / Q000196:embryology; D019902:Chondrocytes / Q000737:chemistry*; D016228:Endothelial Growth Factors / Q000032:analysis* / Q000235:genetics; D006132:Growth Plate / Q000166:cytology*; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D007223:Infant; D008222:Lymphokines / Q000032:analysis* / Q000235:genetics; D020033:Protein Isoforms / Q000032:analysis / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000032:analysis; D012333:RNA, Messenger / Q000032:analysis; D020794:Receptor Protein-Tyrosine Kinases / Q000032:analysis; D017978:Receptors, Growth Factor / Q000032:analysis; D040262:Receptors, Vascular Endothelial Growth Factor; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013977:Tibia / Q000196:embryology / Q000254:growth & development; D042461:Vascular Endothelial Growth Factor A; D040281:Vascular Endothelial Growth Factor Receptor-1; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D008222:Lymphokines; D020033:Protein Isoforms; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D017978:Receptors, Growth Factor; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D020794:Receptor Protein-Tyrosine Kinases; D040262:Receptors, Vascular Endothelial Growth Factor; D040281:Vascular Endothelial Growth Factor Receptor-1