Sp1 interference prevents joint destruction of RA through inhibitory effects of gliostatin

• Project/Area Number: 23592225
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Orthopaedic surgery
• Research Institution: Nagoya City University
• Principal Investigator: NAGAYA Yuko 名古屋市立大学, 医学(系)研究科(研究院), 教授 (90291583)
• Co-Investigator(Kenkyū-buntansha): OTSUKA Takanobu 名古屋市立大学, 大学院医学研究科, 教授 (10185316) ; ASAI Kiyofumi 名古屋市立大学, 大学院医学研究科, 教授 (70212462)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2011: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 関節リウマチ / 滑膜細胞 / グリオスタチン / Sp1 / クロマチン免疫沈降 / チミジンホスホリラーゼ / NF-κB / カルシニューリン阻害剤 / タクロリムス

Research Abstract

Gliostatin/thymidine phosphorylase (GLS/TP) has angiogenic and arthritogenic activities, and aberrant GLS production has been observed in the active synovial membranes of rheumatoid arthritis (RA) patients. The human GLS gene promoter contains at least seven consensus binding sites for the DNA binding protein Sp1. Here we examined whether Sp1 is necessary for GLS production in RA.Mithramycin is an aureolic-acid anti-neoplastic antibiotic used for treating cancer-related hypercalcaemia, leukemia and testicular cancer, which prevents Sp1 binding to its cognate site in DNA by modifying CG sequences. We also studied the effects of the Sp1 inhibitor mithramycin on GLS production in RA fibroblast-like synoviocytes.

Research Products

• [Journal Article] Tumor necrosis factor stimulates osteoclastogenesis from human bone marrow cells under hypoxic conditions. (2014)
  • Author(s): Nomura T, Aoyama M, Waguri-Nagaya Y, Goto Y, Suzuki M, Miyazawa K, Asai K, Goto S.
  • Journal Title: Exp Cell Res Volume: 321 Issue: 2 Pages: 167-177
  • DOI: 10.1016/j.yexcr.2013.11.020
  • Peer Reviewed
• [Journal Article] Cigarette smoke condensate extracts induce IL-1 beta production from rheumatoid arthritis patient-derived synoviocytes, but not osteoarthritis patient-derived synoviocytes, through aryl hydrocarbon receptor-dependent NF-kappa B activation and novel NF-kappa B sites. (2013)
  • Author(s): Adachi M, Okamoto S, Chujyo S, Arakawa T, Yokoyama M, Yamada K, Hayashi A, Akita K, Takeno M, Ito S, Takii T, Waguri-Nagaya Y, Otsuka T, Hayakawa K, Miyazawa K, Onozaki K.
  • Journal Title: J Interferon & Cytokine Research Volume: 33 Issue: 6 Pages: 297-307
  • DOI: 10.1089/jir.2012.0107
  • Peer Reviewed
• [Journal Article] The Sp1 transcription factor is essential for the expression of gliostatin/thymidine phosphorylase in rheumatoid fibroblast-like synoviocytes. (2012)
  • Author(s): Ikuta K, Waguri-Nagaya Y, Kikuchi K, Yamagami T, Nozaki M, Aoyama M, Asai K,Otsuka T.
  • Journal Title: Arthritis Res Ther. Volume: 14 Issue: 2
  • DOI: 10.1186/ar3811
  • Peer Reviewed
• [Journal Article] Comparative risk of common peroneal nerve injury in far anteromedial portal drilling and transtibial drilling in anatomicaldouble-bundle ACL reconstruction. (2012)
  • Author(s): Otani M, Nozaki M, Kobayashi M, Goto H, Tawada K, Waguri-Nagaya Y, Okamoto H, Iguchi H, Watanabe N, Otsuka T.
  • Journal Title: Knee Surg Sports Traumatol Arthrosc Volume: 20 Issue: 5 Pages: 838-843
  • DOI: 10.1007/s00167-011-1632-8
  • Peer Reviewed
• [Journal Article] FK506inhibition of gliostatin/thymidine phosphorylase production induced by tumornecrosis factor-α in rheumatoid fibroblast-like synoviocytes. (2011)
  • Author(s): Yamagami T, Waguri-Nagaya Y, Ikuta K, Aoyama M, Asai K, Otsuka T.
  • Journal Title: Rheumatol Int. Volume: 31 Issue: 7 Pages: 903-9
  • DOI: 10.1007/s00296-010-1411-8
  • Peer Reviewed
• [Journal Article] FK506 inhibition of gliostatin/thymidine phosphorylase production induced by tumor necrosis factor-α in rheumatoid fibroblast-like synoviocytes. (2011)
  • Author(s): T Yamagami, Waguri-Nagaya Y, Ikuta K, Aoyama M, Asai K, Otsuka T.
  • Journal Title: Rheumatol Int (Clinical and Experimental Investigations) Volume: 37 Pages: 903-909
  • Peer Reviewed
• [Journal Article] Comparative risk of common peroneal nerve injury in far anteromedial portal drilling and transtibial drilling in anatomicaldouble-bundle ACL reconstruction. (2011)
  • Author(s): Otani M, Nozaki M, Kobayashi M, Goto H, Tawada K, Waguri-Nagaya Y, Okamoto H, Iguchi H, Watanabe N, Otsuka T.
  • Journal Title: Knee Surg Sports Traumatol Arthrosc Volume: in press
  • Peer Reviewed
• [Presentation] Gliostatin regulates vascular endothelial growth-factor production in human fibroblast-like synoviocytes (2014)
  • Author(s): Kawaguchi Y, Waguri-Nagaya Y, Tatematsu N, Kobayashi M, Goto H, Nozaki M, Ikuta K, Aoyama M, Asai K, Otsuka T
  • Organizer: Annual European Congress of Rheumatology
  • Place of Presentation: Le Palais des Congres de Paris, France (発表確定)
• [Presentation] The importance of gliostatin as an indicator of disease activity in patients with rheumatoid arthritis (2014)
  • Author(s): Ikuta K, Waguri-Nagaya Y, Tatematsu N, Kawaguchi Y, Kobayashi M, Aoyama M, Asai K, Otsuka T
  • Organizer: Annual European Congress of Rheumatology
  • Place of Presentation: Le Palais des Congres de Paris, France (発表確定)
• [Presentation] The importance of gliostatin as an indicator of disease activity in patients with rheumatoid arthritis. (2014)
  • Author(s): Ikuta K, Waguri-Nagaya Y, Tatematsu N, Kawaguchi Y, Kobayashi M, Aoyama M, Asai K, Otsuka T.
  • Organizer: Annual European Congress of Rheumatology
  • Place of Presentation: Le Palais des Congres de Paris (France)
• [Presentation] Gliostatin regulates vascular endothelial growth-factor production in human fibroblast-like synoviocytes. (2014)
  • Author(s): Kawaguchi Y, Waguri-Nagaya Y, Tatematsu N, Kobayashi M, Goto H, Nozaki M, Ikuta K, Aoyama M, Asai K, Otsuka T.
  • Organizer: Annual European Congress of Rheumatology
  • Place of Presentation: Le Palais des Congres de Paris (France)
• [Presentation] Aquaporin expression in the synovial tissues of patients with osteoarthritis and rheumatoid arthritis (2013)
  • Author(s): Tatematsu N, Waguri-Nagaya Y, Nagahara M, Ikuta K, Aoyama M, Asai K, Otsuka T
  • Organizer: Annual European Congress of Rheumatology
  • Place of Presentation: Feria de Madrid, Spain
  • Year and Date: 2013-06-13
• [Presentation] The Sp1 transcription factor is essential for the expression of gliostatin/thymidine phosphorylase in rheumatoid fibroblast-like synoviocytes (2013)
  • Author(s): Ikuta K, Waguri-Nagaya Y, Terazawa M, Aoyama M, Asai K, Kobayashi M, Otsuka T
  • Organizer: Annual European Congress of Rheumatology
  • Place of Presentation: Feria de Madrid, Spain
  • Year and Date: 2013-06-13
• [Presentation] 転写因子Sp1は関節リウマチ由来線維芽細胞様滑膜細胞におけるグリオスタチン発現を制御する (2013)
  • Author(s): 生田憲史,永谷祐子,菊池可絵,青山峰芳,浅井清文,小林正明,大塚隆信
  • Organizer: 第57回日本リウマチ学会
  • Place of Presentation: 京都国際会議場
  • Year and Date: 2013-04-18
• [Presentation] The Sp1 transcription factor is essential for the expression of gliostatin/thymidine phosphorylase in rheumatoid fibroblast-like synoviocytes. (2013)
  • Author(s): Ikuta K, Waguri-Nagaya Y, Terazawa M, Aoyama M, Asai K, Kobayashi M, Otsuka T.
  • Organizer: Annual European Congress of Rheumatology
  • Place of Presentation: Feria de Madrid (Spain)
• [Presentation] Aquaporin expression in the synovial tissues of patients with osteoarthritis and rheumatoid arthritis. (2013)
  • Author(s): Tatematsu N, Waguri-Nagaya Y, Nagahara M, Ikuta K, Aoyama M, Asai K, Otsuka T.
  • Organizer: Annual European Congress of Rheumatology
  • Place of Presentation: Feria de Madrid (Spain)
• [Presentation] 関節リウマチと変形性関節症での膝関節軟骨におけるgliostatin/thymidine phosphorylaseの発現分布 (2012)
  • Author(s): 山上貴也, 永谷祐子,生田憲史,青山峰芳,浅井清文, 大塚隆信
  • Organizer: 第27回日本整形外科基礎学術集会
  • Place of Presentation: 名古屋国際会議場
  • Year and Date: 2012-10-27
• [Presentation] 関節リウマチサイトカインネットワークにおけるグリオスタチン (2012)
  • Author(s): 生田憲史,永谷祐子,菊池可絵,青山峰芳,浅井清文,小林正明,大塚隆信
  • Organizer: 第27回日本整形外科基礎学術集会
  • Place of Presentation: 名古屋国際会議場
  • Year and Date: 2012-10-26
• [Presentation] 関節リウマチ サイトカインネットワークにおけるグリオスタチン. (2012)
  • Author(s): 生田憲史，永谷祐子，菊池可絵, 青山峰芳，浅井清文, 小林正明，大塚隆信.
  • Organizer: 第27回日本整形外科基礎学術集会
  • Place of Presentation: 名古屋国際会議場（名古屋）
• [Presentation] 関節リウマチと変形性関節症での膝関節軟骨におけるgliostatin/thymidine phosphorylaseの発現分布. (2012)
  • Author(s): 山上貴也, 永谷祐子，生田憲史，青山峰芳，浅井清文,大塚隆信.
  • Organizer: 第27回日本整形外科基礎学術集会
  • Place of Presentation: 名古屋国際会議場（名古屋）
• [Presentation] 悪性リンパ腫化学療法後に深部感染が再燃するも人工肘関節を温存し得た関節リウマチ患者の1例. (2012)
  • Author(s): 生田憲史，永谷祐子, 多和田兼章, 野崎正浩, 渡邊宣之, 後藤英之, 井口普敬,小林正明, 大塚隆信.
  • Organizer: 第42回日本人工関節学会
  • Place of Presentation: 沖縄コンベンションセンター(宜野湾市)
• [Presentation] p38 MAPKが関節リウマチ線維芽細胞様滑膜細胞におけるグリオスタチン発現に関与する (2011)
  • Author(s): 生田憲史,永谷祐子,菊池可絵,大塚隆信,青山峰芳,浅井清文
  • Organizer: 第26回日本整形外科学会基礎学術集会
  • Place of Presentation: 前橋ベイシア文化ホール
  • Year and Date: 2011-10-21
• [Presentation] Sp1転写因子が関節リウマチ線維芽細胞様滑膜細胞でのグリオスタチン発現に関連する (2011)
  • Author(s): 生田憲史,永谷祐子,菊池可絵,小林正明,大塚隆信,青山峰芳,浅井清文
  • Organizer: 第55回日本リウマチ学会
  • Place of Presentation: 神戸国際会議場
  • Year and Date: 2011-07-24
• [Presentation] FK506 inhibited gliostatin production in patients with rheumatoid arthritis and synoviocytes stumulated by TNF-α (2011)
  • Author(s): Ikuta K, Nagaya Y, Yamagami T, Kobayashi M, Nozaki M, Goto H, Aoyama M, Asai K, Otsuka T.
  • Organizer: the SICOT XXV Triennial World Congress
  • Place of Presentation: Prague, Czech Republic
• [Presentation] Limitations of the gap balancing technique in creating rectangular flexion gap in total knee arthroplasy. (2011)
  • Author(s): Masahiro Nozaki, Masaaki Kobayashi, Yuko Nagaya, Hideyki Goto, Hideki Okamoto, Nobuyuki Watanabe, Hirotaka Iguchi, Takanobu Otsuka.
  • Organizer: the SICOT XXV Triennial World Congress
  • Place of Presentation: Prague, Czech Republic
• [Presentation] Primary total hip arhtroplasty using metasul anatomical porous replacement (APR) cup:ten to fifteen years results. (2011)
  • Author(s): Nobuyuki Watanabe, Hirotaka Iguchi, Masaaki Kobayashi, Isato Sekiya, Yuko Nagaya, Hideyki Goto, Masahiro Nozaki, Hideki Okamoto, Satona Murakami, Takanobu Otsuka.
  • Organizer: the SICOT XXV Triennial World Congress
  • Place of Presentation: Prague, Czech Republic
• [Presentation] Clinical results of new method for benign bone tumors in femora - arthroscopic curettage. (2011)
  • Author(s): Masaaki Kobayashi, Isato Sekiya, Yuko Nagaya, Hideyki Goto, Hideki, Masahiro Nozaki, Hirotaka Iguchi, Nobuyuki Watanabe, Hideki Okamoto, Takanobu Otsuka.
  • Organizer: the SICOT XXV Triennial World Congress
  • Place of Presentation: Prague, Czech Republic
• [Presentation] p38 MAPKが関節リウマチ線維芽細胞様滑膜細胞におけるグリオスタチン発現に関与する (2011)
  • Author(s): 生田憲史，永谷祐子，菊池可絵，大塚隆信，青山峰芳，浅井清文
  • Organizer: 第26回日本整形外科学会基礎学術集会
  • Place of Presentation: 前橋(群馬県）
• [Presentation] Sp1転写因子が関節リウマチ線維芽細胞様滑膜細胞でのグリオスタチン発現に関連する (2011)
  • Author(s): 生田憲史，永谷祐子，菊池可絵，小林正明，大塚隆信，青山峰芳，浅井清文.
  • Organizer: 第55回日本リウマチ学会
  • Place of Presentation: 神戸（兵庫県）
• [Book] 達人はこうみる四肢関節画像診断関節リウマチ(RA)とRA類似疾患の画像診断 (2013)
  • Author(s): 永谷祐子, 大塚隆信
  • Publisher: Monthly Book Orthopaedics (26 (5))