Targeting the synovial angiogenesis as a novel treatment approach to osteoarthritis

Abstract

Synovitis is a key feature in osteoarthritis and is associated with symptom severity. Synovial membrane inflammation is secondary to cartilage degradation which occurs in the early stage and is located adjacent to cartilage damage. This inflammation is characterized by the invasion and activation of macrophages and lymphocytes, the release in the joint cavity of large amounts of pro-inflammatory and procatabolic mediators, and by a local increase of synovial membrane vascularity. This latter process plays an important role in the chronicity of the inflammatory reaction by facilitating the invasion of the synovium by immune cells. Therefore, synovial membrane angiogenesis represents a key target for the treatment of osteoarthritis. This paper is a narrative review of the literature referenced in PubMed during the past 5 years. It addresses in particular three questions. What are the mechanisms involved in synovium blood vessels invasion? Are current medications effective in controlling blood vessels formation and invasion? What are the perspectives of research in this area?

Comparison of periprosthetic tissues in knee and hip joints: differential expression of CCL3 and DC-STAMP in total knee and hip arthroplasty and similar cytokine profiles in primary knee and hip osteoarthritis

“…Interestingly, we observed similar profile of investigated inflammatory and osteoclastogenic molecules in OA, irrespective of the affected joint. In conjunction with a recent emphasis on the role of synovium in the pathogenesis of OA 56 , our findings support the hypothesis on similar mechanisms contributing to the development of osteoarthritic synovium in knee and hip joints.…”

Bone marrow lesions in hip osteoarthritis are characterized by increased bone turnover and enhanced angiogenesis

“…In this context, it is interesting that dual inhibition of angiogenesis and nerve growth by anti-NGF therapy has shown promising results in phase II and III trials with respect to knee or hip OA pain and function 29 . Inhibition of synovial angiogenesis has also been suggested as a novel treatment approach to control inflammation and pain in OA by reducing damage to subchondral bone and cartilage 30 .…”

Low-grade inflammation as a key mediator of the pathogenesis of osteoarthritis

“…Several therapies that inhibit VEGF have proven beneficial in animal models of arthritis, and their anti-inflammatory and anti-angiogenic effects in OA are now being evaluated in clinical trials 109 . Intraarticular administration of recombinant FGF18 is also being investigated in individuals with OA (TABLE 1).…”