RT Journal Article
SR Electronic
T1 Arthritogenicity of annexin VII revealed by phosphoproteomics of rheumatoid synoviocytes
JF Annals of the Rheumatic Diseases
JO Ann Rheum Dis
FD BMJ Publishing Group Ltd and European League Against Rheumatism
SP 1489
OP 1495
DO 10.1136/ard.2010.145524
VO 70
IS 8
A1 Kosuke Matsuo
A1 Mitsumi Arito
A1 Koji Noyori
A1 Hiroshi Nakamura
A1 Manae S Kurokawa
A1 Kayo Masuko
A1 Kazuki Okamoto
A1 Kouhei Nagai
A1 Naoya Suematsu
A1 Kazuo Yudoh
A1 Moroe Beppu
A1 Tomoyuki Saito
A1 Tomohiro Kato
YR 2011
UL http://ard.bmj.com/content/70/8/1489.abstract
AB Objective To identify novel proteins involved in the pathogenesis of rheumatoid arthritis (RA) and to characterise the identified proteins based on pathogenic and therapeutic aspects. Methods The authors applied differential phosphoproteomic analysis to articular synoviocytes between RA and osteoarthritis (OA) to identify proteins differently phosphorylated between RA and OA. Focusing on annexin VII (Anx7), one of the highly phosphorylated proteins in RA, the authors prepared Anx7-transgenic C57BL/6 (Anx7-Tg-B6) mice to evaluate their susceptibility to collagen-induced arthritis (CIA). In addition, the authors examined the effect of anti-Anx7 antibodies (Abs) on CIA and serum levels of cytokines in wild-type DBA/1J mice, which are known to be susceptible to CIA, and in Anx7-Tg-B6 mice. In vitro, the authors examined the effect of the Anx7 knockdown by small interfering RNA on the secretion of cytokines in rheumatoid synoviocytes and the human synovial sarcoma cell line SW982. Results The Anx7 transgene altered the CIA-resistant B6 mice to CIA-susceptible ones. The Abs treatment suppressed CIA even in the wild-type DBA/1J mice. The serum levels of cytokines including interleukin 6 (IL-6) and TNFα were not altered by the Abs treatment in vivo. On the other hand, the knockdown of Anx7 by small interfering RNA caused downregulation of IL-8 secretion in vitro. Conclusions These results indicate that Anx7 participates in the pathogenesis of RA partly through the secretion of IL-8. The study data have demonstrated the pathogenic roles and therapeutic significance of Anx7 in RA for the first time.