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Regulatory T-cell signaling in periodontitis

Research Project

Project/Area Number 17K11676
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Pathobiological dentistry/Dental radiology
Research InstitutionKagoshima University

Principal Investigator

Tomokazu Ohnishi  鹿児島大学, 医歯学域歯学系, 准教授 (30244247)

Co-Investigator(Kenkyū-buntansha) 松口 徹也  鹿児島大学, 医歯学域歯学系, 教授 (10303629)
柿元 協子  鹿児島大学, 医歯学総合研究科, 客員研究員 (40274849)
楠山 譲二  鹿児島大学, 医歯学総合研究科, 客員研究員 (70596105)
Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords歯周炎 / FOXP3 / JNK / Treg / periodontitis / TGF-β / T細胞 / iTreg / DUSP16 / 免疫 / 感染 / 炎症 / ヘルパーT細胞
Outline of Final Research Achievements

We generated transgenic mice (dnDUSP16-Tg) that express the dominant negative (dn) of Dual specific phosphatase 16 (DUSP16), a specific dephosphatase of JNK, in a T cell-specific manner to increase the activity of JNK. dnDUSP16-Tg was subjected to experimental periodontitis, and the loss of alveolar bone was suppressed compared to wild-type mice. In addition, the presence of regulatory T cells (iTreg), which suppress the immune system, was found in periodontal tissues with periodontitis. Analysis of spleen lymphocytes from these mice showed that the ratio of iTreg was higher than that of wild-type mice, and TGF-beta facilitated the differentiation of iTreg.

Academic Significance and Societal Importance of the Research Achievements

歯肉炎を含めると歯周病は30歳以上の日本国民の2/3以上が罹患している最も多い成人病の一つである。歯を失う原因として最も多いのが歯周病の一つである歯周炎である。歯周炎は歯周ポケットの歯周菌により誘導された歯肉炎が進行し、過剰な免疫反応が歯槽骨を含む歯周組織の破壊が起こす疾患である。よって、その免疫を制御する制御性Tリンパ球への分化と歯周炎の進行の指標である歯槽骨吸収の関係性を探ることは有意義なことである。特に本研究では制御性Tリンパ球への分化をシグナル分子であるJNKの脱リン酸化酵素が歯槽骨破壊と関連することを示した。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (15 results)

All 2020 2019 2018 2017

All Journal Article (10 results) (of which Int'l Joint Research: 5 results,  Peer Reviewed: 10 results,  Open Access: 2 results,  Acknowledgement Compliant: 1 results) Presentation (5 results)

  • [Journal Article] Glut1 expression is increased by p53 reduction to switch metabolism to glycolysis during osteoblast differentiation2020

    • Author(s)
      Ohnishi Tomokazu、Kusuyama Joji、Bandow Kenjiro、Matsuguchi Tetsuya
    • Journal Title

      Biochemical Journal

      Volume: - Issue: 10 Pages: 1795-1811

    • DOI

      10.1042/bcj20190888

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] CXCL13 is a differentiation- and hypoxia-induced adipocytokine that exacerbates the inflammatory phenotype of adipocytes through PHLPP1 induction.2019

    • Author(s)
      Kusuyama J, Bandow K, Ohnishi T, Amir MS, Shima K, Semba I, Matsuguchi T.
    • Journal Title

      Biochem J

      Volume: 476 Issue: 22 Pages: 3533-3548

    • DOI

      10.1042/bcj20190709

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] BMP9 prevents induction of osteopontin in JNK-inactivated osteoblasts via Hey1-Id4 interaction.2019

    • Author(s)
      Kusuyama J, Seong C, Nakamura T, Ohnishi T, Amir MS, Shima K, Semba I, Noguchi K, Matsuguchi T.
    • Journal Title

      Int J Biochem Cell Biol.

      Volume: 116 Pages: 105617-105617

    • DOI

      10.1016/j.biocel.2019.105614

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] BMP9 directly induces rapid GSK3-β phosphorylation in a Wnt-independent manner through class I PI3K-Akt axis in osteoblasts.2019

    • Author(s)
      Eiraku N, Chiba N, Nakamura T, Amir MS, Seong CH, Ohnishi T, Kusuyama J, Noguchi K, Matsuguchi T.
    • Journal Title

      FASEB Journal

      Volume: 33 Issue: 11 Pages: 12124-12134

    • DOI

      10.1096/fj.201900733rr

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] JNK inactivation suppresses osteogenic differentiation, but robustly induces osteopontin expression in osteoblasts through the induction of inhibitor of DNA binding 4 (Id4).2019

    • Author(s)
      Kusuyama J, Amir MS, Albertson BG, Bandow K, Ohnishi T, Nakamura T, Noguchi K, Shima K, Semba I, Matsuguchi T.
    • Journal Title

      FASEB J.

      Volume: - Issue: 6 Pages: 7331-7347

    • DOI

      10.1096/fj.201802465r

    • Related Report
      2019 Annual Research Report 2018 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Low-intensity pulsed ultrasound promotes bone morphogenic protein 9-induced osteogenesis and suppresses inhibitory effects of inflammatory cytokines on cellular responses via Rho-associated kinase 1 in human periodontal ligament fibroblasts.2019

    • Author(s)
      Kusuyama J, Nakamura T, Ohnishi T, Albertson BG, Ebe Y, Eiraku N, Noguchi K, Matsuguchi T.
    • Journal Title

      J Cell Biochem

      Volume: - Issue: 9 Pages: 14657-14669

    • DOI

      10.1002/jcb.28727

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Spleen tyrosine kinase influences the early stages of multilineage differentiation of bone marrow stromal cell lines by regulating phospholipase C gamma activities.2018

    • Author(s)
      Kusuyama J,, Kamisono A, ChangHwan S, Amir MS, Bandow K, Eiraku N, Ohnishi T, Matsuguchi T.
    • Journal Title

      J Cell Physiol.

      Volume: 233 Issue: 3 Pages: 2549-2559

    • DOI

      10.1002/jcp.26130

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Constitutive activation of p46JNK2 is indispensable for C/EBPδ induction in the initial stage of adipogenic differentiation.2017

    • Author(s)
      Kusuyama J, Ohnishi T, Bandow K, Amir MS, Shima K, Semba I, Matsuguchi T.
    • Journal Title

      Biochem J.

      Volume: 474 Issue: 20 Pages: 3421-3437

    • DOI

      10.1042/bcj20170332

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Low-Intensity Pulsed Ultrasound (LIPUS) Promotes BMP9-Induced Osteogenesis and Suppresses Inflammatory Responses in Human Periodontal Ligament-Derived Stem Cells.2017

    • Author(s)
      Kusuyama J, Nakamura T, Ohnishi T, Eiraku N, Noguchi K, Matsuguchi T.
    • Journal Title

      J Orthop Trauma.

      Volume: 31 Issue: 7 Pages: S4-S4

    • DOI

      10.1097/01.bot.0000520897.92470.70

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Osteopontin inhibits osteoblast responsiveness through the downregulation of focal adhesion kinase mediated by the induction of low molecular weight-protein tyrosine phosphatase.2017

    • Author(s)
      Kusuyama J., Bandow K., Ohnishi T., Hisadome M., Shima K., Semba I., Matsuguchi T.
    • Journal Title

      Mol. Biol. Cell.

      Volume: Mar 22 Issue: 10 Pages: 10-07

    • DOI

      10.1091/mbc.e16-10-0716

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] Glycolysis inhibition increases apoptotic protein expressions via ubiquitin/proteasome system in primary osteoblasts at the early differentiation stage.2019

    • Author(s)
      大西智和 千葉紀香 松口徹也
    • Organizer
      第61回歯科基礎医学会学術大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] BMP9 の Class1 PI3K-Akt 経路を介した直接的な骨芽細胞分化誘導2019

    • Author(s)
      榮樂菜保子  , 大西智和 , 千葉紀香  , 野口和行 , 松口徹也
    • Organizer
      第 1 回南九州歯学会総会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 実験的歯周炎マウスモデルにおけるP. gingivalis 感染の糖尿病性腎症に及ぼす影響2019

    • Author(s)
      大西智和 , 千葉紀香 , 松口徹也
    • Organizer
      第 1 回南九州歯学会総会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Inhibition of keratinocyte response to interferon-g by ultraviolet-B irradiation is mediated through ER-stress2019

    • Author(s)
      Tomokazu Ohnishi, Norika Chiba, Nahoko Eiraku, Amir Subhan, Tetsuya Matsuguchi
    • Organizer
      日本生化学会
    • Related Report
      2018 Research-status Report
  • [Presentation] Inhibition of glycolysis disturbs ubiquitin-proteasome system in primary osteoblasts2017

    • Author(s)
      Tomokazu Ohnishi, Joji Kusuyama, Nahoko Eiraku, Muhammad Subhan Amir, Tetsuya Matsuguchi
    • Organizer
      日本生化学会 日本分子生物学会 合同大会
    • Related Report
      2017 Research-status Report

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Published: 2017-04-28   Modified: 2021-02-19  

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