Vascular Endothelial Growth Factor in Cartilage Development and Osteoarthritis

Sci Rep. 2017 Oct 12;7(1):13027. doi: 10.1038/s41598-017-13417-w.


Genome wide studies indicate that vascular endothelial growth factor A (VEGF) is associated with osteoarthritis (OA), and increased VEGF expression correlates with increased disease severity. VEGF is also a chondrocyte survival factor during development and essential for bone formation, skeletal growth and postnatal homeostasis. This raises questions of how the important embryonic and postnatal functions of VEGF can be reconciled with an apparently destructive role in OA. Addressing these questions, we find that VEGF acts as a survival factor in growth plate chondrocytes during development but only up until a few weeks after birth in mice. It is also required for postnatal differentiation of articular chondrocytes and the timely ossification of bones in joint regions. In surgically induced knee OA in mice, a model of post-traumatic OA in humans, increased expression of VEGF is associated with catabolic processes in chondrocytes and synovial cells. Conditional knock-down of Vegf attenuates induced OA. Intra-articular anti-VEGF antibodies suppress OA progression, reduce levels of phosphorylated VEGFR2 in articular chondrocytes and synovial cells and reduce levels of phosphorylated VEGFR1 in dorsal root ganglia. Finally, oral administration of the VEGFR2 kinase inhibitor Vandetanib attenuates OA progression.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Administration, Oral
  • Animals
  • Antibodies / pharmacology
  • Bone Development
  • Cartilage, Articular / embryology*
  • Cartilage, Articular / pathology*
  • Cell Differentiation
  • Cell Lineage
  • Chondrocytes / metabolism
  • Collagen Type II / metabolism
  • Disease Progression
  • Endothelium / metabolism
  • Female
  • Gene Deletion
  • Gene Expression Regulation
  • Growth Plate / metabolism
  • Growth Plate / pathology
  • Integrases / metabolism
  • Knee Joint / pathology
  • Mice, Inbred C57BL
  • Neovascularization, Physiologic
  • Osteoarthritis / metabolism*
  • Osteoarthritis / pathology
  • Osteogenesis
  • Protein Kinase Inhibitors / administration & dosage
  • Protein Kinase Inhibitors / pharmacology
  • Vascular Endothelial Growth Factor A / deficiency
  • Vascular Endothelial Growth Factor A / genetics
  • Vascular Endothelial Growth Factor A / metabolism*
  • Vascular Endothelial Growth Factor Receptor-2 / antagonists & inhibitors
  • Vascular Endothelial Growth Factor Receptor-2 / metabolism


  • Antibodies
  • Collagen Type II
  • Protein Kinase Inhibitors
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factor Receptor-2
  • Cre recombinase
  • Integrases