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Extended report
Arthritogenicity of annexin VII revealed by phosphoproteomics of rheumatoid synoviocytes
  1. Kosuke Matsuo1,2,
  2. Mitsumi Arito1,
  3. Koji Noyori2,
  4. Hiroshi Nakamura1,3,
  5. Manae S Kurokawa1,
  6. Kayo Masuko1,
  7. Kazuki Okamoto1,
  8. Kouhei Nagai1,
  9. Naoya Suematsu1,
  10. Kazuo Yudoh4,
  11. Moroe Beppu5,
  12. Tomoyuki Saito2,
  13. Tomohiro Kato1
  1. 1Clinical Proteomics and Molecular Medicine, St Marianna University Graduate School of Medicine, Kawasaki, Kanagawa, Japan
  2. 2Department of Orthopedic Surgery, Yokohama City University, Yokohama, Kanagawa, Japan
  3. 3Department of Joint diseases and Rheumatism, Nippon Medical School, Tokyo, Japan
  4. 4Institute of Medical Science, St Marianna University School of Medicine, Kawasaki, Kanagawa, Japan
  5. 5Department of Orthopaedic Surgery, St Marianna University School of Medicine, Kawasaki, Kanagawa, Japan
  1. Correspondence to Dr Tomohiro Kato, Clinical Proteomics and Molecular Medicine, St Marianna University Graduate School of Medicine, 2-16-1, Sugao, Miyamae, Kawasaki, Kanagawa 216–8512, Japan; t3kato{at}


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.

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  • KM and MA contributed equally to this work.

  • Funding This study was supported in part by a grant-in aid from Ministry of Education, Culture, Sports, Science and Technology of Japan.

  • Competing interests None.

  • Patient consent Obtained.

  • Ethics approval This study was conducted with the approval of the St Marianna University School of Medicine.

  • Provenance and peer review Not commissioned; externally peer reviewed.