Mechanisms and targets of angiogenesis and nerve growth in osteoarthritis

Nat Rev Rheumatol. 2012 May 29;8(7):390-8. doi: 10.1038/nrrheum.2012.80.


During osteoarthritis (OA), angiogenesis is increased in the synovium, osteophytes and menisci and leads to ossification in osteophytes and the deep layers of articular cartilage. Angiogenic and antiangiogenic factors might both be upregulated in the osteoarthritic joint; however, vascular growth predominates, and the articular cartilage loses its resistance to vascularization. In addition, blood vessel growth is increased at--and disrupts--the osteochondral junction. Angiogenesis in this location is dependent on the creation of channels from subchondral bone spaces into noncalcified articular cartilage. Inflammation drives synovial angiogenesis through macrophage activation. Blood vessel and nerve growth are linked by common pathways that involve the release of proangiogenic factors, such as vascular endothelial growth factor, β-nerve growth factor and neuropeptides. Proangiogenic factors might also stimulate nerve growth, and molecules produced by vascular cells could both stimulate and guide nerve growth. As sensory nerves grow along new blood vessels in osteoarthritic joints, they eventually penetrate noncalcified articular cartilage, osteophytes and the inner regions of menisci. Angiogenesis could, therefore, contribute to structural damage and pain in OA and provide potential targets for new treatments.

Publication types

  • Review

MeSH terms

  • Angiogenesis Inducing Agents / metabolism
  • Antirheumatic Agents / pharmacology
  • Blood Vessels / metabolism
  • Blood Vessels / pathology
  • Cartilage, Articular / blood supply
  • Cartilage, Articular / pathology*
  • Chondrocytes / metabolism
  • Chondrocytes / pathology
  • Humans
  • Neovascularization, Pathologic / drug therapy
  • Neovascularization, Pathologic / metabolism
  • Neovascularization, Pathologic / pathology*
  • Nerve Growth Factor / metabolism
  • Neural Pathways / growth & development
  • Neural Pathways / metabolism
  • Neural Pathways / pathology*
  • Neuropeptides / metabolism
  • Osteoarthritis / drug therapy
  • Osteoarthritis / metabolism
  • Osteoarthritis / pathology*
  • Synovial Membrane / blood supply
  • Synovial Membrane / metabolism
  • Synovial Membrane / pathology*
  • Synovitis / metabolism
  • Synovitis / pathology
  • Vascular Endothelial Growth Factor A / metabolism


  • Angiogenesis Inducing Agents
  • Antirheumatic Agents
  • Neuropeptides
  • Vascular Endothelial Growth Factor A
  • Nerve Growth Factor