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.
Angiogenesis contributes to synovitis, osteochondral damage, osteophyte formation and meniscal pathology in patients with osteoarthritis (OA)
Angiogenesis is intimately linked to sensory nerve growth through shared regulatory pathways
Nerve growth along new blood vessels into structures that are normally not innervated could contribute to pain in OA
Inhibition of subchondral bone turnover can prevent osteochondral angiogenesis and reduce pain in animal models of OA
Inhibition of angiogenesis could potentially be used to treat OA
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D. A. Walsh declares that he has acted as a consultant for Pfizer. P. I. Mapp declares no competing interests.
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Mapp, P., Walsh, D. Mechanisms and targets of angiogenesis and nerve growth in osteoarthritis. Nat Rev Rheumatol 8, 390–398 (2012). https://doi.org/10.1038/nrrheum.2012.80
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