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Functional and pathological analyses of inflammatory bone destruction disease by a novel Rab protein

Research Project

Project/Area Number 20H03860
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 57020:Oral pathobiological science-related
Research InstitutionNagasaki University

Principal Investigator

Tsukuba Takayuki  長崎大学, 医歯薬学総合研究科(歯学系), 教授 (30264055)

Co-Investigator(Kenkyū-buntansha) 坂井 詠子  長崎大学, 医歯薬学総合研究科(歯学系), 助教 (10176612)
山口 優  長崎大学, 医歯薬学総合研究科(歯学系), 助教 (50823308)
門脇 知子  長崎大学, 医歯薬学総合研究科(歯学系), 教授 (70336080)
Project Period (FY) 2020-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥17,810,000 (Direct Cost: ¥13,700,000、Indirect Cost: ¥4,110,000)
Fiscal Year 2022: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2021: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2020: ¥7,410,000 (Direct Cost: ¥5,700,000、Indirect Cost: ¥1,710,000)
Keywords炎症性骨破壊疾患 / 細胞内輸送 / 歯周病 / 関節リウマチ / Rab44 / 破骨細胞 / 免疫細胞 / 細胞内小胞輸送
Outline of Research at the Start

歯周病や関節リウマチは代表的な炎症性骨破壊疾患であり、破骨細胞や免疫関連細胞の制御異常により惹起する疾患である。我々は独自の研究から、破骨細胞や免疫関連細胞に発現する新規遺伝子Rab44を見出した。本研究の目的は、炎症性骨破壊疾患におけるRab44の機能を解明することである。そのためにRab44のノックアウトマウスを用いて、歯周病および関節リウマチのモデル実験を行い、野生型マウスとRab44ノックアウトマウスでの病態を比較する。本研究によって免疫細胞や破骨細胞での細胞内小胞輸送の新たな一面を解明し、炎症性骨破壊疾患での役割解析に繋げる。

Outline of Final Research Achievements

Periodontal disease and rheumatoid arthritis are representative inflammatory bone destruction diseases, which are caused by dysregulation of osteoclasts and immune cells. Through our own research, we identified a novel gene, Rab44, that is expressed in osteoclasts and immune cells. However, the function of Rab44 in vivo is unknown. The purpose of this study is to elucidate the function of Rab44 in inflammatory bone destruction diseases. To this end, we used Rab44 knockout mice to model periodontal disease and rheumatoid arthritis, and compared the disease states of wild-type and Rab44-knockout mice. Based on this study, we will elucidate a new aspect of intracellular vesicle trafficking in immune cells and osteoclasts, leading to analysis of its role in inflammatory bone destruction diseases.

Academic Significance and Societal Importance of the Research Achievements

Rab44の研究は破骨細胞の多核化のメカニズムを膜輸送や小胞輸送という切り口から明らかにできる可能性があり、膜輸送と細胞の多核化・巨大化の関係性を明らかにできる可能性が含まれている。さらに骨代謝疾患の新しい病態の解明に繋がる可能性がある。本研究では破骨細胞や免疫系細胞にRab44が特異的に発現しているという我々の独自の知見を基盤にして歯周病や関節リウマチへの応用を視野に入れた研究を展開した。Rab44の分子基盤の解明は破骨細胞の骨吸収機構や免疫細胞でのRab44の解明にとって有益な情報となるだけでなく、新しい骨代謝治療薬あるいは歯周病治療薬への手掛かりになる可能性がある。

Report

(4 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Annual Research Report
  • 2020 Annual Research Report
  • Research Products

    (24 results)

All 2023 2022 2021 2020

All Journal Article (17 results) (of which Int'l Joint Research: 5 results,  Peer Reviewed: 17 results,  Open Access: 17 results) Presentation (7 results) (of which Invited: 1 results)

  • [Journal Article] Rab44 Deficiency Induces Impaired Immune Responses to Nickel Allergy2023

    • Author(s)
      Noguromi Mayuko、Yamaguchi Yu、Sato Keiko、Oyakawa Shun、Okamoto Kuniaki、Murata Hiroshi、Tsukuba Takayuki、Kadowaki Tomoko
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 24 Issue: 2 Pages: 994-994

    • DOI

      10.3390/ijms24020994

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Transposon mutagenesis and genome sequencing identify two novel, tandem genes involved in the colony spreading of Flavobacterium collinsii, isolated from an ayu fish, Plecoglossus altivelis2023

    • Author(s)
      Kondo Yoshio、Ohara Kenichi、Fujii Ryoji、Nakai Yudai、Sato Chikara、Naito Mariko、Tsukuba Takayuki、Kadowaki Tomoko、Sato Keiko
    • Journal Title

      Frontiers in Cellular and Infection Microbiology

      Volume: 13 Pages: 01-16

    • DOI

      10.3389/fcimb.2023.1095919

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Rab34 plays a critical role as a bidirectional regulator of osteoclastogenesis2022

    • Author(s)
      Feng Yunxia、Tran Manh Tien、Lu Yanyin、Htike Kaung、Okusha Yuka、Sogawa Chiharu、Eguchi Takanori、Kadowaki Tomoko、Sakai Eiko、Tsukuba Takayuki、Okamoto Kuniaki
    • Journal Title

      Cell Biochemistry and Function

      Volume: 40 Issue: 3 Pages: 263-277

    • DOI

      10.1002/cbf.3691

    • Related Report
      2022 Annual Research Report 2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Coronin1C is a GDP-specific Rab44 effector that controls osteoclast formation by regulating cell motility in macrophages.2022

    • Author(s)
      Yu Yamaguchi, Tomoko Kadowaki, Nozomi Aibara, Kaname Ohyama, Kuniaki Okamoto, Eiko Sakai and Takayuki Tsukuba
    • Journal Title

      Int. J. Mol. Sci.

      Volume: 23 Issue: 12 Pages: 6619-6619

    • DOI

      10.3390/ijms23126619

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] HSP90 drives the Rab11a-mediated vesicular transport of the cell surface receptors in osteoclasts2022

    • Author(s)
      Tran MT, Okusha Y, Feng Y, Sogawa C, Eguchi T, Kadowaki T, Sakai E, Tsukuba T, Okamoto K
    • Journal Title

      Cell Biochem Funct

      Volume: 40(8) Issue: 8 Pages: 838-855

    • DOI

      10.1002/cbf.3745

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Rab44 isoforms similarly promote lysosomal exocytosis, but exhibit differential localization in mast cells.2021

    • Author(s)
      Kadowaki T, Yamaguchi Y, Ogawa K, Tokuhisa M, Okamoto K, Tsukuba T.
    • Journal Title

      FEBS Open Bio

      Volume: 11 Issue: 4 Pages: 1165-1185

    • DOI

      10.1002/2211-5463.13133

    • Related Report
      2021 Annual Research Report 2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Liquid-phase ASEM imaging of cellular and structural details in cartilage and bone formed during endochondral ossification: Keap1-deficient osteomalacia2021

    • Author(s)
      Sakai E, Sato M, Memtily N, Tsukuba T, Sato C.
    • Journal Title

      Sci Rep.

      Volume: 11 Issue: 1 Pages: 5722-5722

    • DOI

      10.1038/s41598-021-84202-z

    • Related Report
      2021 Annual Research Report 2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] A novel role of HSP90 in regulating osteoclastogenesis by abrogating Rab11b-driven transport2021

    • Author(s)
      Tran Manh Tien、Okusha Yuka、Feng Yunxia、Sogawa Chiharu、Eguchi Takanori、Kadowaki Tomoko、Sakai Eiko、Tsukuba Takayuki、Okamoto Kuniaki
    • Journal Title

      Biochimica et Biophysica Acta (BBA) - Molecular Cell Research

      Volume: 1868 Issue: 10 Pages: 119096-119096

    • DOI

      10.1016/j.bbamcr.2021.119096

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Large Rab GTPases: Novel Membrane Trafficking Regulators with a Calcium Sensor and Functional Domains2021

    • Author(s)
      Tsukuba Takayuki、Yamaguchi Yu、Kadowaki Tomoko
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 22 Issue: 14 Pages: 7691-7691

    • DOI

      10.3390/ijms22147691

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The Role of Cytokines Produced via the NLRP3 Inflammasome in Mouse Macrophages Stimulated with Dental Calculus in Osteoclastogenesis2021

    • Author(s)
      Mae Megumi、Alam Mohammad Ibtehaz、Yamashita Yasunori、Ozaki Yukio、Higuchi Kanako、Ziauddin S. M.、Montenegro Raudales Jorge Luis、Sakai Eiko、Tsukuba Takayuki、Yoshimura Atsutoshi
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 22 Issue: 22 Pages: 12434-12434

    • DOI

      10.3390/ijms222212434

    • NAID

      120007186852

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] (−)-Epigallocatechin-3-gallate inhibits RANKL-induced osteoclastogenesis via downregulation of NFATc1 and suppression of HO-1–HMGB1–RAGE pathway2020

    • Author(s)
      Nishioku T, Kubo T, Kamada T, Okamoto K, Tsukuba T, Uto T, Shoyama Y.
    • Journal Title

      Biomedical Research

      Volume: 41 Issue: 6 Pages: 269-277

    • DOI

      10.2220/biomedres.41.269

    • NAID

      130007948845

    • ISSN
      0388-6107, 1880-313X
    • Year and Date
      2020-12-01
    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] . The Inhibitory Role of Rab11b in Osteoclastogenesis through Triggering Lysosome-Induced Degradation of c-Fms and RANK Surface Receptors.2020

    • Author(s)
      Tran MT, Okusha Y, Feng Y, Morimatsu M, Wei P, Sogawa C, Eguchi T, Kadowaki T, Sakai E, Okamura H, Naruse K, Tsukuba T, Okamoto K
    • Journal Title

      Int. J. Mol. Sci.

      Volume: 21 Issue: 24 Pages: 9352-9352

    • DOI

      10.3390/ijms21249352

    • NAID

      120006952291

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Role of the EF-hand and coiled-coil domains of human Rab44 in localisation and organelle formation.2020

    • Author(s)
      Ogawa K, Kadowaki T, Tokuhisa M, Yamaguchi Y, Umeda M, Tsukuba T.
    • Journal Title

      Sci. Rep.

      Volume: 10 Issue: 1 Pages: 19149-19149

    • DOI

      10.1038/s41598-020-75897-7

    • NAID

      120006988463

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Rab11A Functions as a Negative Regulator of Osteoclastogenesis through Dictating Lysosome-Induced Proteolysis of c-fms and RANK Surface Receptors.2020

    • Author(s)
      Okusha Y, Tran MT, Itagaki M, Sogawa C, Eguchi T, Okui T, Kadowaki T, Sakai E, Tsukuba T, Okamoto K.
    • Journal Title

      Cells

      Volume: 9 Issue: 11 Pages: 2384-2384

    • DOI

      10.3390/cells9112384

    • NAID

      120006941059

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Expression and localisation of Rab44 in immune-related cells change during cell differentiation and stimulation.2020

    • Author(s)
      Tokuhisa M., Kadowaki T., Ogawa K., Yamaguchi Y., Kido MA., Gao W., Umeda M., Tsukuba T.
    • Journal Title

      Sci. Rep.

      Volume: 10 Issue: 1 Pages: 10728-10728

    • DOI

      10.1038/s41598-020-67638-7

    • NAID

      120006988132

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Dimethyl fumarate prevents osteoclastogenesis by decreasing NFATc1 expression, inhibiting of erk and p38 MAPK phosphorylation, and suppressing of HMGB1 release2020

    • Author(s)
      Nishioku T, Kawamoto M, Okizono R, Sakai E, Okamoto K, Tsukuba T.
    • Journal Title

      Biochem Biophys Res Commun.

      Volume: 530 Issue: 2 Pages: 455-461

    • DOI

      10.1016/j.bbrc.2020.05.088

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The large GTPase Rab44 regulates granule exocytosis in mast cells and IgE-mediated anaphylaxis.2020

    • Author(s)
      Kadowaki T, Yamaguchi Y, Kido MA, Abe T, Ogawa K, Tokuhisa M, Gao W, Okamoto K, Kiyonari H, Tsukuba T.
    • Journal Title

      Cell Mol Immunol.

      Volume: 17 Issue: 12 Pages: 1287-1289

    • DOI

      10.1038/s41423-020-0413-z

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] 高分子量Rabタンパク質が制御する筋芽細胞から筋管への分化機構2022

    • Author(s)
      谷本 あゆ子,山口 優,門脇 知子,親川 駿, 坂井 詠子,小野 悠介, 吉田 教明,筑波 隆幸
    • Organizer
      第95回生化学会大会
    • Related Report
      2022 Annual Research Report
  • [Presentation] Coronin1CはGDP特異的Rab44エフェクターでありマクロファージの細胞運動を調節することで破骨細胞形成を制御する2022

    • Author(s)
      山口 優,門脇 知子,相原 希美,大山 要,岡元 邦彰,坂井 詠子,筑波 隆幸
    • Organizer
      第95回生化学会大会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 高分子量Rabタンパク質による筋衛星細胞と筋形成過程に及ぼす影響2022

    • Author(s)
      親川駿、山口優,門脇知子,谷本あゆ子, 坂井詠子,村田比呂司、筑波隆幸
    • Organizer
      第95回生化学会大会
    • Related Report
      2022 Annual Research Report
  • [Presentation] Rufy4はRUNドメインを介して破骨細胞による骨吸収を制御する2022

    • Author(s)
      坂井 詠子, Farhana Fatima, 小栁 悠, 山口 優,筑波 隆幸
    • Organizer
      第95回生化学会大会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 金属アレルギーでの高分子量Gタンパク質Rab44の役割2022

    • Author(s)
      野黒美麻由子、山口優、佐藤啓子、村田比呂司、筑波隆幸、門脇知子
    • Organizer
      第45回分子生物学会年会
    • Related Report
      2022 Annual Research Report
  • [Presentation] Rab44タンパク質による炎症応答制御機構2022

    • Author(s)
      門脇知子、山口 優、佐藤啓子、筑波隆幸
    • Organizer
      第64回歯科基礎医学会学術大会
    • Related Report
      2022 Annual Research Report
  • [Presentation] リソソームとアレルギー疾患制御2020

    • Author(s)
      門脇知子、山口 優、筑波隆幸
    • Organizer
      第62回歯科基礎医学会
    • Related Report
      2020 Annual Research Report
    • Invited

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Published: 2020-04-28   Modified: 2024-01-30  

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