Citrullinated fibronectin inhibits apoptosis and promotes the secretion of pro-inflammatory cytokines in fibroblast-like synoviocytes in rheumatoid arthritis
- Equal contributors
1 Department of Clinical Laboratory, Shanghai East Hospital, School of Medicine, Tong Ji University, 150 Ji Mo Road, Shanghai 200120, PR China
2 Department of General Surgery, Shanghai Zhabei District Central Hospital, 619 Zhong Hua Xin Road, Shanghai 200072, PR China
3 Department of Rheumatology, General Hospital, Ningxia Medical University, 804 Shengli South Road, Yinchuan 750004, PR China
4 Department of Rheumatology, Guanghua Hospital of Integrative Medicine, 540 Xin Hua Road, Shanghai 200052, PR China
Citation and License
Arthritis Research & Therapy 2012, 14:R266 doi:10.1186/ar4112Published: 10 December 2012
Rheumatoid arthritis (RA) is characterized by synovial lining hyperplasia, in which there may be an imbalance between the growth and death of fibroblast-like synoviocytes (FLSs). Antibodies against citrullinated proteins are proposed to induce RA. This study aimed to investigate the pathogenic role of citrullinated fibronectin (cFn) in RA.
The distribution of fibronectin (Fn) and cFn in synovial tissues from RA and osteoarthritis (OA) patients was examined by immunohistochemical and double immunofluorescence analysis. FLSs were isolated from RA and OA patients and treated with Fn or cFn. Apoptosis was detected by flow cytometry and TUNEL assay. The expression of survivin, caspase-3, cyclin-B1, Bcl-2 and Bax was detected by real-time PCR. The secretion of proinflammatory cytokines was measured by ELISA.
Fn formed extracellular aggregates that were specifically citrullinated in synovial tissues of RA patients, but no Fn deposits were observed in those of OA patients. Fn induced the apoptosis of RA and OA FLSs while cFn inhibited the apoptosis of RA and OA FLSs. Fn significantly increased the expression of caspase-3 and decreased the expression of survivin and cyclin-B1 in FLSs from RA and OA patients. cFn significantly increased the expression of survivin in RA FLSs. Furthermore, cFn increased the secretion of TNF-α and IL-1 by FLSs.
cFn plays a potential pathophysiologic role in RA by inhibiting apoptosis and increasing proinflammatory cytokine secretion of FLSs.