Elevated angiogenin levels in synovial fluid from patients with inflammatory arthritis and secretion of angiogenin by cultured synovial fibroblasts

Abstract

SUMMARYAngiogenesis is a key process in the pathogenesis of inflammatory arthritis. Angiogenin is one of the most potent inducers of neovascularization in experimental models in vivo . To look for evidence that angiogenin is involved in inflammatory joint disease, we examined plasma and synovial fluid (SF) samples from rheumatology patients and synovial fibroblast cell culture supernatants. Angiogenin levels were determined by radioimmunoassay and ELISA. Plasma angiogenin concentrations ranged from 96 to 478 ng/ml, with no significant difference between patients and normal controls. In SF, angiogenin concentrations were significantly higher in patients with acute or chronic synovitis (rheumatoid arthritis (RA): median, 104 ng/ml; range 13-748, n = 14; crystal-induced arthritis (CIA): median, 149 ng/ml; range, 37-616, n = 14, and other chronic inflammatory arthritis: median, 42 ng/ml; range, 15-205; n = 9) than in the 18 patients with osteoarthritis (OA) (median, 20 ng/ml; range 8-116) ( P < 0·0001, ANOVA ). Angiogenin levels in SF from RA patients in remission with secondary OA were similar to those achieved in primary OA, and decreased in parallel with the resolution of acute gout. Angiogenin protein was released by cultured synovial fibroblasts from OA and RA patients, and reached 1·18 ng/10 6 cells/ day. These data suggest that angiogenin may mediate local inflammation in arthritis via effects on angiogenesis and leucocyte regulation.

Angiogenin expression in the sera and skin of patients with rheumatic diseases

“…First, there was no significant difference in the serum angiogenin levels among normal subjects and patients arterial occlusive disease as well as inflammatory arthritis (21)(22)(23)(24). Our research is the first to measure serum angiogenin levels in patients with PM/DM, SSc and SLE, but we didnot find any significant difference between controls and these patients.…”

A Critical Role for Adrenomedullin-Calcitonin Receptor-Like Receptor in Regulating Rheumatoid Fibroblast-Like Synoviocyte Apoptosis

“…All in vitro experiments were conducted using primary synovial cells cultured between passages 3 and 6. FLS were characterized using a fluorescence-activated cell sorter with anti-5B5 Ab (DakoCytomation), a marker for hyaluronidase (25). Cell confluence and morphology were assessed throughout the experiments by phase-contrast microscopy with collection of microphotographs using a NIKON 995 digital camera.…”

Influence of Extracellular RNAs, Released by Rheumatoid Arthritis Synovial Fibroblasts, on Their Adhesive and Invasive Properties

“…identifying increased RNase5 levels in RA synovial fluids (47). However, the existence of exRNAs as proinflammatory factors was not uncovered yet, such that mechanistic relationships remained elusive at that time.…”