Vascular endothelial growth factor is expressed in human fetal growth cartilage

J Bone Miner Res. 2000 Mar;15(3):534-40. doi: 10.1359/jbmr.2000.15.3.534.


Angiogenesis is a crucial event in endochondral ossification. Chemoattractants and mitogens for endothelial cells (such as basic fibroblast growth factor [bFGF] and transforming growth factor beta [TGF-beta]), which act as local regulators of the process, are synthesized by chondrocytes under several stimuli and in relation to the differentiation stage of the cartilage. Vascular 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 growth plate cartilage of human fetuses (20-22 weeks old) and its expression was demonstrated by reverse-transcription polymerase chain reaction (RT-PCR). Primary culture of human fetal epiphyseal chondrocytes (HFEC) maintained VEGF expression at protein and messenger RNA (mRNA) levels and this expression was stimulated by cartilage-promoting growth factors incorporated into the culture media (rFGF-b, rTGF-beta1, and insulin-like growth factor [rFGF-b] at 50 ng/ml). The conditioned medium (CM) of HFEC stimulated the proliferation of endothelial cells, and this was partially blocked by anti-VEGF antibody. These studies showed VEGF production by chondrocytes of the epiphyseal growth cartilage and suggested a role of this factor in cartilage physiology and the angiogenic process.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alternative Splicing
  • Calcitriol / pharmacology
  • Cartilage / cytology
  • Cartilage / embryology*
  • Cartilage / metabolism
  • Cell Line, Transformed / drug effects
  • Cells, Cultured / metabolism
  • Culture Media, Conditioned
  • DNA Replication / drug effects
  • Endothelial Growth Factors / biosynthesis*
  • Endothelial Growth Factors / genetics
  • Endothelium, Vascular / cytology
  • Epidermal Growth Factor / pharmacology
  • Fetal Proteins / biosynthesis*
  • Fetal Proteins / genetics
  • Fibroblast Growth Factor 2 / pharmacology
  • Gene Expression Regulation, Developmental
  • Gestational Age
  • Growth Plate / blood supply
  • Growth Plate / cytology
  • Growth Plate / embryology*
  • Growth Plate / metabolism
  • Humans
  • Insulin-Like Growth Factor I / pharmacology
  • Insulin-Like Growth Factor II / pharmacology
  • Lymphokines / biosynthesis*
  • Lymphokines / genetics
  • Neovascularization, Physiologic / physiology*
  • RNA, Messenger / biosynthesis
  • Recombinant Proteins / pharmacology
  • Reverse Transcriptase Polymerase Chain Reaction
  • Transforming Growth Factor beta / pharmacology
  • Tretinoin / pharmacology
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors


  • Culture Media, Conditioned
  • Endothelial Growth Factors
  • Fetal Proteins
  • Lymphokines
  • RNA, Messenger
  • Recombinant Proteins
  • Transforming Growth Factor beta
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors
  • Fibroblast Growth Factor 2
  • Tretinoin
  • Epidermal Growth Factor
  • Insulin-Like Growth Factor I
  • Insulin-Like Growth Factor II
  • Calcitriol