The role of Semaphorin 4D in Rheumatoid Arthritis

• Project/Area Number: 25460495
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Experimental pathology
• Research Institution: Osaka University
• Principal Investigator: Ogata Atsushi 大阪大学, 医学(系)研究科(研究院), 招へい教授 (90309451)
• Co-Investigator(Kenkyū-buntansha): TANAKA Toshio 大阪大学, 医学系研究科, 寄付講座教授 (40273651)
• Co-Investigator(Renkei-kenkyūsha): KUMANOGOU Atsushi 大阪大学, 医学系研究科, 教授 (10294125)
• Research Collaborator: YOSHIDA Yuji
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 関節リウマチ / セマフォリン / セマフォリン4D / マウスコラーゲン関節炎 / セマフォリン４D

Outline of Final Research Achievements

It has been reported that semaphorine 4D (Sema4D) is a suppressor of osteogenesis. It may be involved in the pathogenesis of rheumatoid arthritis which presents bone erosion and destruction. According our study, the sera and joint fluids contained higher level of protease ADAMTS-4, and this made shedding of Sema4D from the membrane of CD3+ and CD14+ mononuclear cells resulting in augmentation of Sema4D level in sera and joint fluid. Because arthritis model mice which were injected anti-Sema4D antibody have presented suppression of arthritis, augmented Sema4D may induce bone erosion and destruction in the patients with rheumatoid arthritis.

Research Products

• [Journal Article] 1.Semaphorin 4D contributes to rheumatoid arthritis by inducing inflammatory cytokine production: Pathogenic and therapeutic implications (2015)
  • Author(s): Yoshida Y, Ogata A, Kang S, Ebina K, Shi K, Nojima S, Kimura T, Ito D, Morimoto K, Nishide M, Hosokawa T, Hirano T, Shima Y, Narazaki M, Tsuboi H, Saeki Y, Tomita T, Tanaka T, Kumanogoh A.
  • Journal Title: Arthritis Rheumatol Volume: none Issue: 6 Pages: 1481-1490
  • DOI: 10.1002/art.39086
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] Contribution of Semaphorin 4D (Sema4D): increased soluble Sema4D enhanced RA inflammation and Sema4D antibody inhibited mouse collagen induced arthritis. (2015)
  • Author(s): Yoshida Y, Ogata A, Ebina K, Shi K, Hirano T, Shima Y, Narazaki M, Tanaka T, Tsuboi H,Saeki Y, Tomita T, Kumanogoh A.
  • Organizer: 第５９回日本リウマチ学会総会・学術総会, International Rheumatology Symposium．
  • Place of Presentation: 名古屋
  • Year and Date: 2015-04-23 – 2015-04-25
• [Presentation] Contribution of semaphorin 4D (Sema4D) in rheumatoid arthritis (RA): increased soluble Sema4D enhanced RA inflammation and Sema4D antibody inhibited mouse xollagen arthritis． (2015)
  • Author(s): Yoshida Y, Ogata A, Ebina K, Shi K, Hirano T, Shima Y, Narazaki M, Tanaka T, Tsuboi H, Saeki Y, Tomita T, Kumanogoh A.
  • Organizer: The 59th Annual General Assembly and Scientific Meeting of the Japan College of Rheumatology, International Concurrent Workshop
  • Place of Presentation: Nagoya Japan
  • Year and Date: 2015-04-23
  • Int'l Joint Research
• [Presentation] Soluble Semaphorin 4D in rheumatoid arthritis (2014)
  • Author(s): Yoshida Y, Ogata A, Tomita T, Shima Y, Narazaki M, Tanaka T, Kumanogoh A
  • Organizer: 第５８回日本リウマチ学会総会・学術集会 International Concurrent Workshop
  • Place of Presentation: tokyo
• [Presentation] 可溶性Sema4Dは関節リウマチ患者の血清、関節液で上昇し、疾患活動性と相関する (2014)
  • Author(s): 吉田佑志、緒方篤、冨田哲也、平野亨、嶋良仁、楢崎雅司、田中敏郎、熊ノ郷淳
  • Organizer: 第５８回日本リウマチ学会総会・学術集会
  • Place of Presentation: 東京