The role of Notch on rheumatoid arthritis

• Project/Area Number: 22591085
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: 膠原病・アレルギー・感染症内科学
• Research Institution: Juntendo University
• Principal Investigator: SEKINE Chiyoko 順天堂大学, 医学部, 助教 (40392005)
• Project Period (FY): 2010 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2012: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2011: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2010: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: Notch / 関節リウマチ / 炎症 / 破骨細胞分化 / 血管新生 / リンパ管 / 破骨細胞

Research Abstract

We revealed that Notch2/Delta-like 1 (Dll1) axis promotedosteoclastogenesis but Notch1/Jagged1 axis suppressed it. Actually, blockade of Dll1 suppressed osteoclastogenesis and bone loss in the affected joints of a mouse arthritis model as well as a mouse osteoporosis model while no effect was observed on normal mouse.Therefore, blockade of Dll1 could be a novel target for the treatment of RA.

Research Products

• [Journal Article] Differential regulation of osteoclastogenesis by Notch2/Delta-like 1 and Notch1/Jagged1 axes (2012)
  • Author(s): Sekine C, Koyanagi A, Koyama N, Hozumi K, Chiba S, Yagita H
  • Journal Title: Arthritis Research and Ttherapy Volume: Vol.14 Issue: 2
  • DOI: 10.1186/ar3758
  • Peer Reviewed
• [Journal Article] Expression of Notch receptors and ligands on immature and mature T cells (2012)
  • Author(s): Koyanagi A, Sekine C, Yagita H
  • Journal Title: Biochemical and Biophysical Research Communications Volume: Vol.418 Issue: 4 Pages: 799-805
  • DOI: 10.1016/j.bbrc.2012.01.106
  • Peer Reviewed
• [Presentation] Blockade of Delta-like1 suppresses osteoclastogenesis and arthritis (2011)
  • Author(s): 関根知世子
  • Organizer: 日本免疫学会
  • Place of Presentation: 幕張メッセ(千葉)
  • Year and Date: 2011-11-28
• [Presentation] Blockade of Delta-like1 suppresses osteoclastogenesis and arthritis (2011)
  • Author(s): 関根知世子
  • Organizer: アメリカリウマチ学会(ACR)
  • Place of Presentation: マコーミックプレイスコンベンションセンター(シカゴ)
  • Year and Date: 2011-11-08
• [Presentation] Blockade of Delta-like 1 suppresses osteoclastogenesis and arthritis (2010)
  • Author(s): 関根知世子
  • Organizer: 7^<th> International Conference on Autoimmunity
  • Place of Presentation: GR Ljubljana Exhibition and Convention Centre(スロベニア)
  • Year and Date: 2010-05-10
• [Presentation] Notch signaling is not essential for the development of marginal zone B cells in autoimmune mice
  • Author(s): 関根 知世子
  • Organizer: 8th International Congress on Autoimmunity
  • Place of Presentation: グラナダ展示会議場 （スペイン）