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The mechanism of periodontal tissue destruction by proteases from periodontal bacteria Porpyromonas gingivalis.

Research Project

Project/Area Number 17K11668
Research Category

Grant-in-Aid for Scientific Research (C)

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

Principal Investigator

Nakayama Masaaki  岡山大学, 医歯薬学域, 助教 (10579105)

Co-Investigator(Kenkyū-buntansha) 大森 一弘  岡山大学, 大学病院, 講師 (20549860)
後藤 和義  岡山大学, 医歯薬学域, 助教 (20626593)
大原 直也  岡山大学, 医歯薬学域, 教授 (70223930)
Project Period (FY) 2017-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2020: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2019: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords歯周病菌 / 歯周炎 / ジンジパイン / 炎症応答 / 細胞内シグナル伝達 / 歯周病細菌 / COX-2 / 細胞内カルシウム / 歯周病 / プロスタグランジン / シクロオキシゲナーゼ-2 / 炎症 / Porphyromonas gingivalis / 歯周組織の炎症 / 細胞応答 / 歯周病原細菌
Outline of Final Research Achievements

The purpose of this study is to reveal the molecular mechanism of infection between periodontal pathogenic bacteria and host cells using cellular and molecular biological approaches, and to analyze the function of pathogenic proteases produced by periodontal pathogenic bacteria to clarify the pathogenesis of periodontal disease. In this study, we focused on gingipains, which are cysteine proteases, produced by Porphyromonas gingivalis (P. gingivalis), to elucidate the pathogenesis of periodontal disease infected with P. gingivalis. We examined the host cell response to the molecular mechanism of COX-2 expression by gingipains and showed that activation of two signaling pathways, ERK and IKK, and found that intracellular calcium is required for COX-2 expression and PGE2 production as the upstream factors.

Academic Significance and Societal Importance of the Research Achievements

本研究は歯周病細菌が産生するプロテアーゼが炎症を誘導する因子であることを示す研究である。それを明らかにできれば、プロテアーゼを産生する口腔細菌が歯周病に関与する重要な細菌であることがわかり、プロテアーゼ産生細菌を増やさないようにすることが歯周病予防に努める指標となると思われる。

Report

(6 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (37 results)

All 2022 2021 2020 2019 2018 2017

All Journal Article (10 results) (of which Int'l Joint Research: 4 results,  Peer Reviewed: 10 results,  Open Access: 7 results) Presentation (22 results) (of which Int'l Joint Research: 2 results,  Invited: 3 results) Book (5 results)

  • [Journal Article] The fungal metabolite (+)-terrein abrogates ovariectomy-induced bone loss and receptor activator of nuclear factor-κB ligand-induced osteoclastogenesis by suppressing protein kinase-C α/βII phosphorylation.2021

    • Author(s)
      Kyosuke Sakaida, Kazuhiro Omori, Masaaki Nakayama, Hiroki Mandai, Saki Nakagawa, Hidefumi Sako, Chiaki Kamei, Satoshi Yamamoto, Hiroya Kobayashi, Satoki Ishii, Mitsuaki Ono, Soichiro Ibaragi, Keisuke Yamashiro, Tadashi Yamamoto, Seiji Suga and Shogo Takashiba
    • Journal Title

      Frontiers in Pharmacology

      Volume: 12 Pages: 674366-674366

    • DOI

      10.3389/fphar.2021.674366

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Point mutation in the stop codon of MAV_RS14660 increases the growth rate of Mycobacterium avium subspecies hominissuis2021

    • Author(s)
      Kawakita Tomomi、Mukai Tetsu、Yoshida Mitsunori、Yamada Hiroyuki、Nakayama Masaaki、Miyamoto Yuji、Suzuki Masato、Nakata Noboru、Takii Takemasa、Ryo Akihide、Ohara Naoya、Ato Manabu
    • Journal Title

      Microbiology

      Volume: 167 Issue: 2 Pages: 1-14

    • DOI

      10.1099/mic.0.001007

    • Related Report
      2021 Annual Research Report 2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Attempt of thyX gene silencing and construction of a thyX deleted clone in a Mycobacterium bovis BCG.2021

    • Author(s)
      Yuki Arimura, Yusuke Minato, Takayuki Wada, Masaaki Nakayama, Ayako Ryumon, Nao Hirata, Chie Nakajima, Yasuhiko Suzuki, Manabu Ato, Kazuo Kobayashi, Naoko Ohara, Seiji Iida, Naoya Ohara
    • Journal Title

      Microbiol Immunol

      Volume: 66 Issue: 1 Pages: 10-14

    • DOI

      10.1111/1348-0421.12944

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Comparative Study of the Susceptibility to Oxidative Stress between Two Types of Mycobacterium bovis BCG Tokyo 1722021

    • Author(s)
      Keiichi Taniguchi, Daisuke Hayashi, Naomi Yasuda, Mao Nakayama, Kaori Yazawa, Shouta Ogawa, Yuji Miyatake, Saki Suda, Haruka Tomita, Miki Tokuda, Saotomo Itoh, Jun-Ichi Maeyama, Naoya Ohara, Saburo Yamamoto, Shigeaki Hida, Kikuo Onozaki and Takemasa Takii
    • Journal Title

      mSphere

      Volume: 6 Issue: 2 Pages: 1-11

    • DOI

      10.1128/msphere.00111-21

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Construction and Characterization of the PGN_0296 Mutant of Porphyromonas gingivalis2020

    • Author(s)
      Abu Saleh Muhammad Shahriar, Shintaro Ono, Masaaki Nakayama, Naoko Ohara, Naoya Ohara
    • Journal Title

      Journal of Oral Biosciences

      Volume: 62 Issue: 4 Pages: 322-326

    • DOI

      10.1016/j.job.2020.09.007

    • NAID

      120007163671

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] The Fungal Metabolite (+)-Terrein Abrogates Osteoclast Differentiation via Suppression of the RANKL Signaling Pathway through NFATc12020

    • Author(s)
      S. Nakagawa, K. Omori, M. Nakayama, H. Mandai, S. Yamamoto, H. Kobayashi, H. Sako, K. Sakaida, H. Yoshimura, S. Ishii, S. Ibaragi, K. Hirai, K. Yamashiro, T. Yamamoto, S. Suga
    • Journal Title

      Int. Immunopharmacol

      Volume: 83 Pages: 106429-106429

    • DOI

      10.1016/j.intimp.2020.106429

    • NAID

      120006892916

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Construction and Characterization of a PGN_0297 Mutant of Porphyromonas gingivalis: Evidence of the Contribution of PGN_0297 to Gingipain Activity2019

    • Author(s)
      Shintaro Ono, Masaaki Nakayama, Masato Tachibana, Abu Saleh Muhammad Shahriar, Wang Heling, Shogo Takashiba, and Naoya Ohara
    • Journal Title

      Acta Medica Okayama

      Volume: 73 Issue: 4 Pages: 315-323

    • DOI

      10.18926/AMO/56933

    • NAID

      120006713034

    • URL

      https://ousar.lib.okayama-u.ac.jp/56933

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Fungal metabolite (+)-terrein suppresses IL-6/sIL-6R-induced CSF1 secretion by inhibiting JAK1 phosphorylation in human gingival fibroblasts2018

    • Author(s)
      Satoshi Yamamoto, Kazuhiro Omori, Hiroki Mandai, Masaaki Nakayama, Saki Nakagawa, Hiroya Kobayashi, Tadashi Kunimine, Hiroshi Yoshimura, Kyosuke Sakaida, Hidefumi Sako, Soichiro Ibaragi, Tadashi Yamamoto, Hiroshi Maeda, Seiji Suga, and Shogo Takashiba
    • Journal Title

      Heliyon

      Volume: 4 Issue: 11 Pages: e00979-e00979

    • DOI

      10.1016/j.heliyon.2018.e00979

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Novel function of Porphyromonas gingivalis gingipains in the PI3K/Akt signaling pathway2017

    • Author(s)
      Masaaki Nakayama, Naoya Ohara
    • Journal Title

      Journal of Oral Biosciences

      Volume: 59 Pages: 131-134

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Molecular mechanisms of Porphyromonas gingivalis-host cell interaction on periodontal diseases2017

    • Author(s)
      Masaaki Nakayama, Naoya Ohara
    • Journal Title

      Japanese Dental Science Review,

      Volume: 53 Issue: 4 Pages: 134-140

    • DOI

      10.1016/j.jdsr.2017.06.001

    • NAID

      210000178578

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Presentation] Porphyromonas gingivalis ジンジパインによるCOX-2発現とPGE2産生におけるカルシウムチャネルの役割2022

    • Author(s)
      中山 真彰, 内藤 真理子, 中山 浩次, 大原 直也
    • Organizer
      第95回日本細菌学会総会
    • Related Report
      2021 Annual Research Report
  • [Presentation] Lautropia mirabilisの分離・培養および検出法の確立と分離株の薬剤感受性に関する解析2022

    • Author(s)
      佐藤 あやめ, 中山 真彰, 藤井 伸治, 松岡 賢市, 前田 嘉信, 和田 祟之, 曽我賢彦, 大原 直也
    • Organizer
      第95回日本細菌学会総会
    • Related Report
      2021 Annual Research Report
  • [Presentation] カルシウムチャネルを介したPorphyromonas gingivalis ジンジパインによるCOX-2発現の分子機序2021

    • Author(s)
      中山 真彰, 内藤 真理子, 中山 浩次, 大原 直也
    • Organizer
      第74回日本細菌学会中国・四国支部総会
    • Related Report
      2021 Annual Research Report
  • [Presentation] The molecular mechanism of Porphyromonas gingivalis gingipains-induced COX-2 expression via the calcium channels2021

    • Author(s)
      中山 真彰, 内藤 真理子, 中山 浩次, 大原 直也
    • Organizer
      第63回歯科基礎医学会学術大会
    • Related Report
      2021 Annual Research Report
  • [Presentation] GRIM-19 is a target of mycobacterial Zn2+ metalloprotease 1 and indispensable for NLRP3 inflammasome activation2021

    • Author(s)
      Tomomi Kurane, Masayuki Umemura, Masaaki Nakayama, Naoya Ohara, Goro Matsuzaki, Giichi Takaesu
    • Organizer
      第50回日本免疫学会学術集会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 結核ワクチンBCG Tokyo172のサブタイプ間の酸化ストレス応答の違い2021

    • Author(s)
      谷口恵一, 林大介, 安田直美, 中山真央, 伊藤佐生智, 山本三郎, 大原直也, 肥田重明, 小野嵜菊夫, 瀧井猛将
    • Organizer
      第94回日本細菌学会総会
    • Related Report
      2020 Research-status Report
  • [Presentation] The significant role of Porphyromonas gingivalis “Gingipains” as a virulence factor on periodontal inflammation2020

    • Author(s)
      Masaaki Nakayama
    • Organizer
      Japanese Association for Dental Research(JADR), a Division of the International Association for Dental Research
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Porphyromonas gingivalis gingipainsによるCOX2発現とPGE2産生における細胞内カルシウムの関与2020

    • Author(s)
      中山 真彰, 内藤 真理子, 中山 浩次, 大原 直也
    • Organizer
      第62回歯科基礎医学会学術大会
    • Related Report
      2020 Research-status Report
  • [Presentation] P. gingivalis ジンジパイン誘導性COX-2発現における細胞外カルシウム流入の関与2020

    • Author(s)
      中山 真彰, 内藤 真理子, 中山 浩次, 大原 直也
    • Organizer
      第93回日本細菌学会総会 ポスター発表
    • Related Report
      2019 Research-status Report
  • [Presentation] P. gingivalis ジンジパインによるCOX-2発現誘導における細胞内Ca2+の関与2019

    • Author(s)
      中山 真彰, 内藤 真理子, 中山 浩次, 大原 直也
    • Organizer
      第72回日本細菌学会中国・四国支部総会 口頭発表
    • Related Report
      2019 Research-status Report
  • [Presentation] Involvement of intracellular calcium on Porphyromonas gingivalis gingipains-induced COX-2 expression and PGE2 production2019

    • Author(s)
      中山 真彰, 内藤 真理子, 中山 浩次, 大原 直也
    • Organizer
      第61回歯科基礎医学会学術大会 ポスター発表
    • Related Report
      2019 Research-status Report
  • [Presentation] 歯周病菌が産生するジンジパインによるCOX-2発現におけるカルシウムの役割2019

    • Author(s)
      中山 真彰, 内藤 真理子, 中山 浩次, 大原 直也
    • Organizer
      第92回日本細菌学会総会 ポスター発表
    • Related Report
      2019 Research-status Report
  • [Presentation] Porphyromonas gingivalis ジンジパインのCOX-2発現/PGE2産生の分子機序2018

    • Author(s)
      中山 真彰
    • Organizer
      第71回日本細菌学会関西支部総会 口頭発表
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] P. gingivalisジンジパインによるCOX-2発現とPGE2産生における細胞内Ca2+の重要性2018

    • Author(s)
      中山 真彰, 内藤 真理子, 橘 理人, 中山 浩次, 大原 直也
    • Organizer
      第71回日本細菌学会中国・四国支部総会
    • Related Report
      2018 Research-status Report
  • [Presentation] Porphyromonas gingivalis gingipainsによるMEK/ERK /AP-1およびIKK/NF-kBp65の活性化を介したCOX-2発現およびPGE2産生の誘導機構2018

    • Author(s)
      中山 真彰, 内藤 真理子, 橘 理人, 中山 浩次, 大原 直也
    • Organizer
      第60回歯科基礎医学会学術大会
    • Related Report
      2018 Research-status Report
  • [Presentation] Inhibitory mechanism of JTY3476 expression by JTY3475 in BCG Tokyo2018

    • Author(s)
      Masaaki Nakayama, Kaori Shirasaki, Masato Tachibana, Saburo Yamamoto, Takemasa Takii, Mayuko Okabe, Manabu Ato, Naoya Ohara
    • Organizer
      The 52nd US-Japan Mycobacteria Panel Meeting 2018
    • Related Report
      2017 Research-status Report
  • [Presentation] Porphyromonas gingivalis ジンジパインによる COX-2発現誘導を介したPGE2産生の分子解析2017

    • Author(s)
      中山 真彰, 内藤 真理子, 橘 理人, 中山 浩次, 大原 直也
    • Organizer
      第91回日本細菌学会総会
    • Related Report
      2017 Research-status Report
  • [Presentation] P. gingivalis ジンジパインによるCOX-2発現およびPGE2産生の分子機序2017

    • Author(s)
      中山 真彰, 内藤 真理子, 橘 理人, 中山 浩次, 大原 直也
    • Organizer
      第70回日本細菌学会中国・四国支部総会
    • Related Report
      2017 Research-status Report
  • [Presentation] Porphyromonas gingivalis gingipains induce PGE2 production via COX-2 expression2017

    • Author(s)
      中山 真彰, 橘 理人, 内藤 真理子, 中山 浩次, 大原 直也
    • Organizer
      第59回歯科基礎医学会学術大会
    • Related Report
      2017 Research-status Report
  • [Presentation] Functions of the virulence factor from periodontal pathogens on periodontal diseases2017

    • Author(s)
      Masaaki Nakayama
    • Organizer
      第65回JADR総会・学術大会
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Porphyromonas gingivalis gingipains induce PGE2 production via COX-2 expression by activation of MEK1/2 and NF-kB2017

    • Author(s)
      Masaaki Nakayama, Mariko Naito, Koji Nakayama, Naoya Ohara
    • Organizer
      PgMelbourne2017
    • Related Report
      2017 Research-status Report
  • [Presentation] Porphyromonas gingivalis gingipains disturb Akt signaling pathway via inactivation of PI3K2017

    • Author(s)
      Masaaki Nakayama, Mariko Naito, Koji Nakayama, Naoya Ohara
    • Organizer
      IUMS 2017
    • Related Report
      2017 Research-status Report
  • [Book] アレルギーの臨床-特集「アレルギー疾患とマイクロバイオーム」-口腔細菌叢と疾患ー口腔細菌の病原因子による歯周疾患への影響2019年2月号(2019年1月25日刊行)2018

    • Author(s)
      中山真彰
    • Total Pages
      4
    • Publisher
      北隆館/ニュー・サイエンス社
    • Related Report
      2018 Research-status Report
  • [Book] Biology Topics (BIOLOGICAL TOPICS(基礎系)) 「歯周病細菌の病原性プロテアーゼと歯周炎」BIO Clinica-特集「口腔疾患と慢性炎症」-2018年別冊春20号(2018年9月25日刊行)2018

    • Author(s)
      中山真彰
    • Total Pages
      4
    • Publisher
      北隆館
    • Related Report
      2018 Research-status Report
  • [Book] 月刊「細胞」-特集「口腔疾患のサイエンス」-「歯周組織炎症における歯周病菌の病原性プロテアーゼの機能解析」2018年9月号(2018年8月22日刊行)2018

    • Author(s)
      中山真彰
    • Total Pages
      4
    • Publisher
      北隆館/ニュー・サイエンス社
    • Related Report
      2018 Research-status Report
  • [Book] 月刊「地域ケアリング」-特集「混合介護への期待と課題」-福祉の現場から「歯周病菌が産生するプロテアーゼの歯周疾患における重要性」 北隆館2018年7月号(2018年6月12日刊行)2018

    • Author(s)
      中山真彰
    • Total Pages
      3
    • Publisher
      北隆館
    • Related Report
      2018 Research-status Report
  • [Book] 特集「病原性細菌の制御」ーTopics from special edition「歯周病菌が産生するプロテアーゼの病原性」2017

    • Author(s)
      中山真彰(Topics from special edition)
    • Total Pages
      600
    • Publisher
      北陸館/ニュー・サイエンス社
    • Related Report
      2017 Research-status Report

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Published: 2017-04-28   Modified: 2023-01-30  

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