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Development of time controlled therapy for aged periodontal tissue.

Research Project

Project/Area Number 17H04416
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Periodontology
Research InstitutionOsaka University

Principal Investigator

YAMASHITA MOTOZO  大阪大学, 歯学部附属病院, 講師 (90524984)

Co-Investigator(Kenkyū-buntansha) 山田 聡  東北大学, 歯学研究科, 教授 (40359849)
村上 伸也  大阪大学, 歯学研究科, 教授 (70239490)
北垣 次郎太  大阪大学, 歯学研究科, 招へい教員 (90570292)
Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥17,160,000 (Direct Cost: ¥13,200,000、Indirect Cost: ¥3,960,000)
Fiscal Year 2019: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2018: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2017: ¥8,320,000 (Direct Cost: ¥6,400,000、Indirect Cost: ¥1,920,000)
Keywords老化 / 細胞老化 / マイクロRNA / 歯根膜細胞 / 慢性炎症 / 歯周病 / 加齢 / microRNAs / エクソソーム / 細部老化 / MicroRNA / トランスオミクス / インフラマエイジング / MicroRNAs / エピジェネティクス
Outline of Final Research Achievements

In this study, we examined the dynamics of gene networks along the time axis to clarify the aging processes leading to the chronic inflammation in periodontal tissue. We focused on senescent periodontal ligament cells with epigenetic mutations, and elucidated the regulatory mechanism of cellular senescence by miRNAs, focusing on various cellular functions such as inflammatory response, mitochondrial function, stem cell, and exosome. We found that senescent periodontal ligament cells showed the age dependent characteristic in ECM production, mitochondrial function, and nuclear membrane, which are regulated by senescent periodontal ligament specific miRNAs-mRNAs mechanisms.

Academic Significance and Societal Importance of the Research Achievements

本研究成果により、加齢とともに進行する歯周組織の老化性の慢性炎症の病態の一部が分子レベルで明らかとなった。新規のトランスオミクス解析によるアプローチにより、miRNAsによる細胞老化の制御機構が、細胞代謝、炎症性応答、ミトコンドリア機能、幹細胞能、エクソソームといった老化歯根膜細胞の多様な細胞機能を調節制御していることが示唆された。今後、得られた分子基盤情報を用いて、歯周組織の老化性の慢性炎症病態を「遺伝子―細胞―組織―個体レベル」で検証することで、高齢者の難治の歯周病の病態マーカーの探索、新規の診断、 予防法の樹立が期待される。

Report

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

    (20 results)

All 2019 2018 2017

All Journal Article (2 results) (of which Peer Reviewed: 2 results,  Open Access: 1 results) Presentation (18 results) (of which Int'l Joint Research: 10 results,  Invited: 1 results)

  • [Journal Article] Effects of paraoxonase 1 on the cytodifferentiation and mineralization of periodontal ligament cells.2017

    • Author(s)
      R Masumoto, J Kitagaki, M Matsumoto, S Miyauchi, C Fujihara, M Yamashita, S Yamada, M Kitamura, S Murakami.
    • Journal Title

      J Periodont Res

      Volume: 53(2) Issue: 2 Pages: 200-209

    • DOI

      10.1111/jre.12507

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] エクソームシークエンスによる日本人侵襲性歯周炎の疾患関連遺伝子探索2017

    • Author(s)
      北垣次郎太、枡本梨沙、宮内静香、藤原千春、村上伸也
    • Journal Title

      日本歯周病学会雑誌

      Volume: 59

    • NAID

      130006825064

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Presentation] Analysis of Mitophagy in Senescent HPDL Cell.2019

    • Author(s)
      Yamashita M, Suzuki M, Ikegam K, Nakamura T, Nishikawa A, Hashimoto K, Morikawa T, Miki K, Yanagita M, Kitamura M, Shinya Murakami.
    • Organizer
      13th Asian Pacific Society of Periodontology Meeting
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] MiR-34a Regutates Stem Cell Aging in Periodontal ligament Stem Cells.2019

    • Author(s)
      Ikegami K, Yamashita M, Suzuki M, Nishikawa A, Hashimoto K, Nakamura T, Miki K, Yanagita M, Kitamura M, Murakami S.
    • Organizer
      13th Asian Pacific Society of Periodontology Meeting
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] NMN Improves the Accumulation of ROS in Senescent HPDL Cells2019

    • Author(s)
      Hashimoto K, Yamashita M, Suzuki M, Ikegami K, Nakamura T, Nishikawa A, Morikawa T, Kitamura M, Murakami S
    • Organizer
      4th Meeting of the International Association for Dental Research Asia Pacific Region 2019
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Activation of HSPs Ameliorates the Collagen Production in HPDL Cells2019

    • Author(s)
      Nishikawa A, Yamashita M, Suzuki M, Ikegami K, Nakamura T, Hashimoto K, Morikawa T, Kitamura M, Murakami S
    • Organizer
      4th Meeting of the International Association for Dental Research Asia Pacific Region 2019
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 老化ヒト歯根膜細胞における活性酸素産生に及ぼすマイトファジーの役割2019

    • Author(s)
      鈴木美麻,山下元三,池上久仁子,中村友美,西川有彩,橋本康樹,北村正博,村上伸也
    • Organizer
      日本歯科保存学会春季学術大会(第150回)
    • Related Report
      2019 Annual Research Report
  • [Presentation] Impairment of mitophagy in senescent HPDL cells.2018

    • Author(s)
      Mio SUZUKI, Motozo YAMASHITA, Kuniko IKEGAMI, Tomomi NAKAMURA, Koji MIKI, Manabu YANAGITA, Masahiro KITAMURA, Shinya MURAKAMI
    • Organizer
      96th General Session and Exhibition of the IADR
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Senescence-associated miR-34a accelerates periodontal stem-cell aging by targeting SATB22018

    • Author(s)
      Kuniko Ikegami, Motozo Yamashita, Mio Suzuki, Arisa Nishikawa, Tomomi Nakamura, Koji Miki, Jirouta Kitagaki, Manabu Yanagita, Masahiro Kitamura and Shinya Murakami
    • Organizer
      American Academy of Periodontology (AAP) 104th Annual Meeting
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Optical dissection of the mitophagy dynamics in HPDL cells.2018

    • Author(s)
      Motozo Yamashita, Mio Suzuki, Kuniko Ikegami, Tomomi Nakamura, Arisa Nishikawa, Koji Miki, Manabu Yanagita, Masahiro Kitamura, Shinya Murakami
    • Organizer
      American Academy of Periodontology (AAP) 104th Annual Meeting
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 老化歯根膜細胞におけるマイトファジーの機能解析2018

    • Author(s)
      山下元三、鈴木美麻、池上久仁子、西川有梨沙、橋本康樹、柳田学、北村正博、村上伸也
    • Organizer
      第18回日本再生医療学会総会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Dissection of the mitophagy dynamics in HPDL cells by fluorescent probe.2018

    • Author(s)
      Mio Suzuki, Motozo Yamashita, Kuniko Ikegami, Tomomi Nakamura, Arisa Nishikawa, Kouki Hashimoto, Koji Miki, Manabu Yanagita, Masahiro Kitamura, Shinya Murakami
    • Organizer
      第66回国際歯科研究学会日本部会総会・学術大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Analysis of cellular senescence in periodontal disease2017

    • Author(s)
      Motozo Yamashita
    • Organizer
      THE 7TH JAPAN-THAILAND KOREA JOINT SYMPOSIUM
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Failure of mitophagy in senescent HPDL cells2017

    • Author(s)
      M Suzuki, M Yamashita, K Ikegami, T Nakamura, K Miki, M Yanagita, M Kitamura, S Murakami
    • Organizer
      第65回国際歯科研究学会日本部会総会・学術大会 JADR2017
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] miR-34a inhibits osteoblastic differentiation of senescent HPDL by targeting SATB22017

    • Author(s)
      K Ikegami
    • Organizer
      第65回国際歯科研究学会日本部会総会・学術大会 JADR2017
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] ヒト老化歯根膜細胞におけるmicroRNA-34a-SATB2を介した硬組織形成制御2017

    • Author(s)
      池上 久仁子,山下 元三,鈴木 美麻,三木 康史,北垣 次郎太,柳田 学,北村 正博,村上 伸也
    • Organizer
      第38回日本炎症・再生医学会
    • Related Report
      2017 Annual Research Report
  • [Presentation] ゲノムワイドアプローチを用いた日本人における侵襲性歯周炎の疾患関連遺伝子探索2017

    • Author(s)
      桝本 梨沙、北垣 次郎太、松本 昌大、宮内 静香、小笹 匡雄、東山 弥生、竹立 匡秀、藤原 千春、山下 元三、山田 聡、北村 正博、村上 伸也
    • Organizer
      第147回 歯科保存学会秋季学術大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] ヒト老化歯根膜細胞におけるマイトファジーの機能低下2017

    • Author(s)
      山下 元三、鈴木 美麻、池上 久仁子、中村 友美、西川 有彩、北村 正博、村上 伸也
    • Organizer
      第40回 日本分子生物学会年会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 日本人における侵襲性歯周炎の疾患関連遺伝子探索2017

    • Author(s)
      桝本 梨沙、北垣 次郎太、松本 昌大、宮内 静香、藤原 千春、黒田 智子、田内 拓史、小笹 匡雄、柏木 陽一郎、沢田 啓吾、山下 元三、柳田 学、竹立 匡秀、山田 聡、野崎 剛徳、北村 正博、村上 伸也
    • Organizer
      第60回 秋季日本歯周病学会学術大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] ヒト老化歯根膜細胞におけるmicro-RNA-34a SATB2を介した硬組織形成制御2017

    • Author(s)
      池上 久仁子、山下 元三、中村 友美、鈴木 美麻、西川 有彩、平沼 麻央、三木 康史、北垣 次郎太、柳田 学、北村 正博、村上 伸也
    • Organizer
      第60回 秋季日本歯周病学会学術大会
    • Related Report
      2017 Annual Research Report

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

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