Therapeutic strategy for rheumatoid arthritis with signal cascade control of gliostatin
Project/Area Number |
16K10913
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Orthopaedic surgery
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Research Institution | Nagoya City University |
Principal Investigator |
Kobayashi Masaki 名古屋市立大学, 大学院医学研究科, 研究員 (20254287)
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Co-Investigator(Kenkyū-buntansha) |
浅井 清文 名古屋市立大学, 大学院医学研究科, 教授 (70212462)
永谷 祐子 名古屋市立大学, 大学院医学研究科, 教授 (90291583)
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Project Period (FY) |
2016-04-01 – 2019-03-31
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Project Status |
Completed (Fiscal Year 2018)
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Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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Keywords | 関節リウマチ / 滑膜細胞 / グリオスタチン / マトリックスメタロプロテイナーゼ / チミジンホスホリラーゼ / ヤヌスキナーゼ / Sp1 / プロモーター / マトリックスメタロプロテアーゼ / シグナル伝達 |
Outline of Final Research Achievements |
We found for the first time that gliostatin is closely involved in the pathogenesis of rheumatoid arthritis. In this study, the goal is to apply the signal cascade control of gliostatin to the treatment of rheumatoid arthritis. We have searched for signal cascade regulators of gliostatin. There are seven Sp1 binding sites in the gliostatin promoter region, and the expression of gliostatin was inhibited by inhibiting Sp1. The knock-on effects were examined using mithramycin, which is an Sp1 transcription factor inhibitor. We also clarified that matrix metalloproteinases-1, 3, 9, 13 that induce cartilage destruction were suppressed by mithramycin.
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Academic Significance and Societal Importance of the Research Achievements |
関節リウマチの治療はこの10年で劇的に進歩し、発症早期からの抗リウマチ薬、生物学的製剤、低分子シグナル伝達阻害剤の導入により、治療は寛解をめざすものになった。しかしながら未だいずれの治療にも反応しない薬剤耐性難治性患者や炎症が鎮静化されたにも関わらず骨びらんの進行がみられる患者が存在する。 本研究によって、グリオスタチンが新たな治療標的となることが明らかとなった。グリオスタチンの抑制によって骨軟骨破壊に関与するマトリックスプロテアーゼが抑制することから、変形性関節症の進展抑制にも応用可能と考える。
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Report
(4 results)
Research Products
(22 results)
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[Journal Article] Treatment of aneurysmal bone cysts using endoscopic curettage2018
Author(s)
Aiba H, Kobayashi M, Waguri-Nagaya Y, Goto H, Mizutani J, Yamada S, Okamoto H, Nozaki M, Mitsui H, Miwa S, Kobayashi M, Endo K, Saito S, Goto T, Otsuka T.
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Journal Title
BMC Musculoskelet Disord
Volume: 19
Issue: 1
Pages: 268-268
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Treatment of simple bone cysts using endoscopic curettage: a case series analysis2018
Author(s)
Aiba H, Kobayashi M, Waguri-Nagaya Y, Goto H, Mizutani J, Yamada S, Okamoto H, Nozaki M, Mitsui H, Miwa S, Kobayashi M, Endo K, Saito S, Goto T, Otsuka T.
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Journal Title
J Orthop Surg Res
Volume: 13
Issue: 1
Pages: 168-168
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Comparison of quantitative evaluation between cutaneous and transosseous inertial sensors in anterior cruciate ligament deficient knee: A cadaveric study.2017
Author(s)
Murase A, Nozaki M, Kobayashi M, Goto H, Yasuma S, Takenaga T, Nagaya Y, Mizutani J, Okamoto H, Iguchi H, Otsuka T.
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Journal Title
J Orthop Sci
Volume: 22
Issue: 5
Pages: 874-879
DOI
Related Report
Peer Reviewed
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[Journal Article] Expression and subcellular localization of AT motif binding factor 1 in colon tumours.2017
Author(s)
Kataoka H, Miura Y, Kawaguchi M, Suzuki S, Okamoto Y, Ozeki K, Shimura T, Mizoshita T, Kubota E, Tanida S, Takahashi S, Asai K, Joh T.
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Journal Title
Mol Med Rep
Volume: 16
Issue: 3
Pages: 3095-3102
DOI
Related Report
Peer Reviewed
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[Journal Article] Do Mesenchymal Stem Cells Derived From Atypical Lipomatous Tumors Have Greater Differentiation Potency Than Cells From Normal Adipose Tissues?2017
Author(s)
Inatani H, Yamamoto N, Hayashi K, Kimura H, Takeuchi A, Miwa S, Higuchi T, Abe K, Taniguchi Y, Yamada S, Asai K, Otsuka T, Tsuchiya H.
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Journal Title
Clin Orthop Relat Res
Volume: 印刷中
Issue: 6
Pages: 1693-1701
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
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[Presentation] Sp1 inhibitor modulates the autocrine action of gliostatin/thymidine phosphorylase (GLS/TYMP) in rheumatoid fibroblast-like synoviocytes.2016
Author(s)
Tatematsu N, Waguri-Nagaya Y, Kawaguchi Y, Ikuta K, Kobayashi M, Goto H, Nozaki M, Aoyama M, Asai K, Otsuka T.
Organizer
Annual European Congress of Rheumatology (EULAR2016)
Place of Presentation
ExCel London, London (United Kingdom)
Year and Date
2016-06-08
Related Report
Int'l Joint Research
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[Presentation] Sp1 interference prevents joint destruction of RA through inhibitory effects of gliostatin and matrix metalloproteinase-3.2016
Author(s)
Ikuta K, Kawaguchi Y, Waguri-Nagaya Y, Tatematsu N, Kobayashi M, Goto H, Nozaki M, Aoyama M, Asai K, Otsuka T.
Organizer
Annual European Congress of Rheumatology (EULAR2016)
Place of Presentation
ExCel London, London (United Kingdom)
Year and Date
2016-06-08
Related Report
Int'l Joint Research
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[Presentation] The JAK inhibitor (Tofacitinib) inhibits TNF-induced gliostatin/thymidine phosphorylase expression in human fibroblast-like synoviocytes.2016
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 (EULAR2016)
Place of Presentation
ExCel London, London (United Kingdom)
Year and Date
2016-06-08
Related Report
Int'l Joint Research
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[Presentation] Anterolateral ligament controls rotational instability as a secondary restraint in ACL deficient knee2016
Author(s)
Yasuma S, Nozaki M, Murase A, Kobayashi M, Sakai H, Goto H, Mitsui H, Nagaya Y, Iguchi H, Otsuka T
Organizer
17th ESSKA Congress
Place of Presentation
Centre Convencions Internacional Barcelona, Barcelona (Spain)
Year and Date
2016-05-04
Related Report
Int'l Joint Research
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