The study of bone destruction mechanism of rheumatoid arthritis by synoviolin

• Project/Area Number: 26461478
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Collagenous pathology/Allergology
• Research Institution: St. Marianna University School of Medicine
• Principal Investigator: YAGISHITA Naoko 聖マリアンナ医科大学, 医学研究科, 講師 (40367389)
• Co-Investigator(Kenkyū-buntansha): 荒谷 聡子 東京医科大学, 医学部, 講師 (40387064) ; 中島 利博 東京医科大学, 医学部, 教授 (90260752) ; 藤田 英俊 東京医科大学, 医学部, 講師 (90571802)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2015: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
• Keywords: 遺伝子 / タンパク質 / 動物 / 関節リウマチ / 滑膜細胞 / 小胞体関連分解 / 骨代謝

Outline of Final Research Achievements

The symptoms of rheumatoid arthritis (RA) are based on the many processes. We recently cloned Synoviolin as an overexpressing molecule in rheumatoid synovium, and has been verifying its critical roles in RA. In this study, we investigated the role of synoviolin in bone and cartilage using Synoviolin conditional knockout mice and showed that Synoviolin has a crucial role in cartilage.

Research Products

• [Journal Article] 関節リウマチ発症因子シノビオリン (2017)
  • Author(s): 八木下尚子, 中島利博.
  • Journal Title: アレルギーの臨床 Volume: 37(2) Pages: 94-100
  • Acknowledgement Compliant
• [Journal Article] 関節リウマチ発症因子シノビオリン (2016)
  • Author(s): 八木下尚子, 中島利博.
  • Journal Title: アレルギーの臨床 Volume: 36(13) Pages: 84-90
  • Acknowledgement Compliant
• [Journal Article] 関節リウマチ発症因子シノビオリン (2016)
  • Author(s): 八木下尚子, 中島利博
  • Journal Title: BIO Clinica 慢性炎症と疾患 Volume: 5(3) Pages: 137-143
  • Acknowledgement Compliant
• [Journal Article] Inhibitory effects of ubiquitination of synoviolin by PADI4 (2016)
  • Author(s): *Aratani S, Fujita H, Yagishita N, Yamano Y, Okubo Y, Nishioka K, Nakajima T
  • Journal Title: Mol. Med. Rep. in press Volume: -
  • Peer Reviewed
• [Journal Article] A case of fibromyalgia involving pain throughout the body treated with site-specific targeted pain control. (2016)
  • Author(s): Nakajima F, Aratani S, Fujita H, Nakatani K, Makita K, Nakajima T
  • Journal Title: Springerplus Volume: 5 Issue: 1 Pages: 1027-1027
  • DOI: 10.1186/s40064-016-2572-z
  • Peer Reviewed / Open Access
• [Journal Article] Mitochondrial Ubiquitin Ligase Activator of NF-κB (MULAN) regulates NF-κB signaling in ER stress-stimulated cells. (2016)
  • Author(s): Fujita H, Aratani S, Fujii R, Yamano Y, Yagishita N, Araya N, Izumi T, Azakami K, Hasegawa D, Nishioka K and Nakajima T
  • Journal Title: Int J Mol Med. Volume: 37 Issue: 6 Pages: 1611-1618
  • DOI: 10.3892/ijmm.2016.2566
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] NAD(P)H quinone oxidoreductase 1 inhibits the proteasomal degradation of homocysteine-inducible endoplasmic reticulum protein. (2016)
  • Author(s): Maeda T, Tanabe-Fujimura C, Fujita Y Abe C, Nanakida Y, Zou K, Liu J, Liu S, Nakajima T, Komano H.
  • Journal Title: Biochem Biophys Res Commun Volume: 473 Issue: 4 Pages: 1276-1280
  • DOI: 10.1016/j.bbrc.2016.04.057
  • Peer Reviewed
• [Journal Article] The E3 ligase synoviolin controls body weight and mitochondrial biogenesis through negative regulation of PGC-1β. (2015)
  • Author(s): Fujita H, Yagishita N, Aratani S, Saito-Fujita T, Morota S, Yamano Y, Hansson MJ, Inazu M, Kokuba H, Sudo K, Sato E, Kawahara K, Nakajima F, Hasegawa D, Higuchi I, Sato T, Araya N, Usui C, Nishioka K, Nakatani Y, Maruyama I, Usui M, Hara N, Uchino H, Elmer E, Nishioka K, Nakajima T.
  • Journal Title: EMBO J. Volume: 34 Issue: 8 Pages: 1042-55
  • DOI: 10.15252/embj.201489897
  • Peer Reviewed / Open Access
• [Journal Article] Synoviolin inhibitor LS-102 reduces endoplasmic reticulum stress-induced collagen secretion in an in vitro model of stress-related interstitial pneumonia. (2015)
  • Author(s): Nakajima F, Aratani S, Fujita H, Yagishita N, Ichinose S, Makita K, Setoguchi Y, Nakajima T.
  • Journal Title: Int J Mol Med. Volume: 35 Issue: 1 Pages: 110-6
  • DOI: 10.3892/ijmm.2014.1984
  • Peer Reviewed / Open Access
• [Journal Article] Hrd1 suppresses Nrf2-mediated cellular protection during liver cirrhosis. (2014)
  • Author(s): Wu T, Zhao F, Gao B, Tan C, Yagishita N, Nakajima T, Wong PK, Chapman E, Fang D, Zhang DD.
  • Journal Title: Genes Dev Volume: 28(7) Issue: 7 Pages: 708-722
  • DOI: 10.1101/gad.238246.114
  • Peer Reviewed / Open Access
• [Presentation] 関節リウマチにおける転写後修飾による多重化シグナル調節機構の解析。 (2016)
  • Author(s): 荒谷聡子、藤田英俊、八木下尚子*、山野嘉久*、西岡久寿樹、中島利博
  • Organizer: 第 3 回 JCR ベーシックリサーチカンファレンス
  • Place of Presentation: （アキバホール）東京都千代田区
  • Year and Date: 2016-10-14
• [Presentation] リウマチ発症因子シノビオリンによる新規エネルギー代謝機構の解明。 (2016)
  • Author(s): 藤田英俊、荒谷聡子、八木下尚子*、山野嘉久*、須藤カツ子*、内野博之、西岡久寿樹、中島利博
  • Organizer: 第 3 回 JCR ベーシックリサーチカンファレンス
  • Place of Presentation: （アキバホール）東京都千代田区
  • Year and Date: 2016-10-14
• [Presentation] シノビオリンが拓く慢性炎症・関節リウマチの病態メカニズムと新規治療法の開発。 (2016)
  • Author(s): 中島利博
  • Organizer: 第 31 回日本整形外科学会基礎学術集会
  • Place of Presentation: 福岡国際会議場（福岡県福岡市）
  • Year and Date: 2016-10-13
• [Presentation] シノビオリン阻害剤の探索。 (2016)
  • Author(s): 藤田英俊、荒谷聡子、西岡久寿樹、中島利博
  • Organizer: 日本線維筋痛症学会第 8 回学術集会
  • Place of Presentation: （KFC Hall&Rooms)東京都墨田区
  • Year and Date: 2016-09-17
• [Presentation] マウスモデルを用いたシノビオリン阻害活性を有する天然物の効果の検証。 (2016)
  • Author(s): 藤田英俊、荒谷聡子、西岡久寿樹、中島利博
  • Organizer: 日本線維筋痛症学会第 8 回学術集会
  • Place of Presentation: (KFC Hall&Rooms)東京都墨田区
  • Year and Date: 2016-09-17
• [Presentation] ヒトにおけるシノビオリン阻害剤の効果の検証。 (2016)
  • Author(s): 藤田英俊、荒谷聡子、西岡久寿樹、中島利博
  • Organizer: 日本線維筋痛症学会第 8 回学術集会
  • Place of Presentation: (KFCHall&Rooms)東京都墨田区
  • Year and Date: 2016-09-17
• [Presentation] 新規自己炎症症候群モデルマウスの樹立とシノビオリン阻害剤の効果。 (2016)
  • Author(s): 中島 利博
  • Organizer: 第 17 回 運動器科学研究会
  • Place of Presentation: (大阪大学中之島センター）大阪府大阪市
  • Year and Date: 2016-09-02
• [Presentation] リウマチ発症因子シノビオリンによるエネルギー代謝調節の解明。 (2016)
  • Author(s): 藤田英俊
  • Organizer: 第17 回 運動器科学研究会
  • Place of Presentation: （大阪大学中之島センター）大阪府大阪市
  • Year and Date: 2016-09-02
• [Presentation] シノビオリン阻害剤の実用化に向けて。 (2016)
  • Author(s): 荒谷聡子
  • Organizer: 第 17 回 運動器科学研究会
  • Place of Presentation: （大阪大学中之島センター）大阪府大阪市
  • Year and Date: 2016-09-02
• [Presentation] Synoviolin, as a novel factor for understanding obesity and metabolic disorders based on chronic inflammation (2016)
  • Author(s): Aratani S, Nakajima T
  • Organizer: International Conference on Obesity and Chronic Diseases (ICOCD-2016)
  • Place of Presentation: Las Vegas(USA)
  • Year and Date: 2016-07-25
  • Int'l Joint Research
• [Presentation] E3 Ubiquitin ligase synoviolin inhibitors has effects on obesity (2016)
  • Author(s): Aratani S, Fujita H, Yagishita N*, Yokota M, Nishioka K, Nakajima T
  • Organizer: International Conference on Obesity and Chronic Diseases (ICOCD-2016)
  • Place of Presentation: Las Vegas(USA)
  • Year and Date: 2016-07-25
  • Int'l Joint Research
• [Presentation] シノビオリン阻害剤の実用化に向けて。 (2016)
  • Author(s): 荒谷聡子、藤田英俊、八木下尚子*、中島若巳、西岡久寿樹、中島利博
  • Organizer: 第 5 回医薬工 3 大学包括連携推進シンポジウム
  • Place of Presentation: (東京医科大学病院）東京都新宿区
  • Year and Date: 2016-06-18
• [Presentation] Synoviolin is a key regulator in chronic inflammation (2016)
  • Author(s): 藤田英俊、荒谷聡子、須藤カツ子、稲津正人、原直美、内野博之、西岡久寿樹、中島利博
  • Organizer: 第 5 回医薬工 3 大学包括連携推進シンポジウム
  • Place of Presentation: (東京医科大学病院）東京都新宿区
  • Year and Date: 2016-06-18
• [Presentation] Study on Clinical-Functional Peculiarities Assessment of Rheumatic Fheumatic Fever in the Kyrgyz Republic (2016)
  • Author(s): Nazgul Omurzakova*, Nakajima T
  • Organizer: The World Congress of Cardiology and Cardiovascular Health (WCC 2016)
  • Place of Presentation: Mexico City(Mexico)
  • Year and Date: 2016-06-04
  • Int'l Joint Research
• [Presentation] E3 ユビキチン化酵素シノビリオン阻害剤の臨床応用への可能性。 (2016)
  • Author(s): 荒谷聡子、藤田英俊、西岡久寿樹、中島利博
  • Organizer: 第 177 回東京医科大学医学会総会
  • Place of Presentation: (東京医科大学病院）東京都新宿区
  • Year and Date: 2016-06-04
• [Presentation] Synoviolin, as a new stellar factor for understanding chronic inflammation. (2016)
  • Author(s): Nakajima T
  • Organizer: MOSCOW INTERNATIONAL FORUM OF BONES AND JOINTS DISORDERS/THE INTERNATIONAL SCHOOL CONFERENCE (ISC)
  • Place of Presentation: Moscow(russia)
  • Year and Date: 2016-04-18
  • Int'l Joint Research
• [Presentation] The role of E3 ubiquitin ligase Synoviolin in bone destruction of rheumatoid arthritis. (2014)
  • Author(s): Yagishita N, Aratani S, Fujita H, Yamano Y, Nishioka K, Nakajima T.
  • Organizer: 第58回日本リウマチ学会総会・学術集会
  • Place of Presentation: 東京都（港区）〔グランドプリンスホテル新高輪〕
  • Year and Date: 2014-04-24 – 2014-04-26
• [Book] New Developments in the Pathogenesis of Rheumatoid Arthritis (2017)
  • Author(s): Synoviolin is a Novel Pathogeniicc Factor of Arthropathy and Chronic Inflammattiion.
  • Total Pages: 162
  • Publisher: INTECH
• [Remarks] http://nanchiken.jp/byouin/
• [Remarks] 聖マリアンナ医科大学 難病治療研究センター
  • URL: http://nanchiken.jp/
• [Remarks] 聖マリアンナ医科大学難病治療研究センター 病因・病態解析部門
  • URL: http://nanchiken.jp/byouin/achievement/