Arthritis & Rheumatism, Volume 62,
November 2010 Abstract Supplement
Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Atlanta, Georgia November 6-11, 2010.
Angiopoietin-Like 4 Is Expressed in Human Synovial Fibroblasts and Expression Is Increased in Response to TGF.
Fall2, Ndate, Frederick2, Malinda, Grom1, Alexei A., Thornton3, Sherry
We previously identified angiopoietin-like 4 (Angptl4) as a novel angiogenic protein that is highly increased in early inflammatory stages of collagen-induced arthritis. The present study determines the expression of Angptl4 mRNA in human synovium and the factor(s) regulating its expression.
Quantification of Angptl4 mRNA levels in synovial tissues was performed by RNase protection analysis. JIA (juvenile idiopathic arthritis) synovial fibroblast cultures were generated from joint replacement synovial tissues. Synovial fibroblast cultures were treated for 2 hours with systemic JIA (sJIA) synovial fluid (SF) or TGF-b, with or without the addition of recombinant human TGF-bRI kinase inhibitor (TbRI Inhibitor). RNA was isolated and Angptl4, IL-1b and GAPDH mRNA levels quantified by realtime RTPCR.
Angptl4 is expressed at higher levels in rheumatoid arthritis (RA) and JIA than in osteoarthritis (OA) synovial tissues. JIA synovial fibroblasts express Angptl4 mRNA, which increases dramatically in the presence of systemic JIA (sJIA) SF. Treatment of JIA synovial fibroblasts with TGF-b shows a dramatic increase in Angptl4 expression that is nullified in the presence of TbRI Inhibitor. Angptl4 mRNA expression in response to SF is also dramatically diminished in the presence of TbRI Inhibitor.
Angptl4 is expressed in human arthritic synovium, suggesting a role for Angptl4 in human arthritic disease. The expression of Angptl4 is highly increased in JIA synovial fibroblasts in response to systemic JIA SF, and is abrogated by inhibition of TGF-bRI signaling, suggesting that TGF-b is a major mediator of Angptl4 expression in inflammatory arthritis.
To cite this abstract, please use the following information:
Fall, Ndate, Frederick, Malinda, Grom, Alexei A., Thornton, Sherry; Angiopoietin-Like 4 Is Expressed in Human Synovial Fibroblasts and Expression Is Increased in Response to TGF. [abstract]. Arthritis Rheum 2010;62 Suppl 10 :244