Angiogenesis in the synovium and at the osteochondral junction in osteoarthritis

Abstract

Objectives: We hypothesised that osteochondral and synovial angiogenesis in osteoarthritis (OA) are independent processes. We investigated whether indices of osteochondral and synovial angiogenesis display different relationships with synovitis, disease severity and chondrocalcinosis in patients with OA. Design: Synovium and medial tibial plateaux were obtained from 62 patients undergoing total knee joint replacement for OA (18 [29%] had chondrocalcinosis) and from 31 recently deceased people with no evidence of joint pathology post-mortem (PM). Vascular endothelium, proliferating endothelial cells (ECs) and macrophages were quantified by immunohistochemistry for CD34, CD31/Ki67 and CD14, respectively. Grades were assigned for radiographic and histological OA disease severity, clinical disease activity and histological synovitis (based on cellular content of the synovium). Results: Blood vessels breached the tidemark in 60% of patients with OA and 20% of PM controls. Osteochondral vascular density increased with increasing cartilage severity and clinical disease activity scores, but not with synovitis. Synovial EC proliferation, inflammation and macrophage infiltration were higher in OA than in PM controls. Synovial angiogenesis indices increased with increasing histological synovitis, but were not related to osteochondral vascular density or other indices of OA disease severity. OA changes were more severe in patients with concurrent chondrocalcinosis. Chondrocalcinosis was not associated with increased angiogenesis or histological synovitis beyond that seen in OA alone. Conclusion: Osteochondral and synovial angiogenesis appear to be independent processes. Osteochondral vascularity is associated with the severity of OA cartilage changes and clinical disease activity, whereas synovial angiogenesis is associated with histological synovitis. Modulation of osteochondral and synovial angiogenesis may differentially affect OA disease.