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The role of extracellular vesicles of oral bacteria in systemic disease

Research Project

Project/Area Number 19H04051
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 59040:Nutrition science and health science-related
Research InstitutionOkayama University

Principal Investigator

Okamura Hirohiko  岡山大学, 医歯薬学域, 教授 (20380024)

Co-Investigator(Kenkyū-buntansha) 江口 傑徳  岡山大学, 医歯薬学域, 講師 (20457229)
宝田 剛志  岡山大学, 医歯薬学域, 教授 (30377428)
吉田 賀弥  徳島大学, 大学院医歯薬学研究部(歯学域), 准教授 (60363157)
池亀 美華  岡山大学, 医歯薬学域, 准教授 (70282986)
江國 大輔  岡山大学, 医歯薬学域, 准教授 (70346443)
伊原木 聰一郎  岡山大学, 医歯薬学域, 准教授 (80549866)
Project Period (FY) 2019-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥17,160,000 (Direct Cost: ¥13,200,000、Indirect Cost: ¥3,960,000)
Fiscal Year 2021: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2020: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
Fiscal Year 2019: ¥6,630,000 (Direct Cost: ¥5,100,000、Indirect Cost: ¥1,530,000)
Keywords歯周病 / 細胞外分泌小胞 / 肝臓 / 糖尿病 / 歯周病原菌 / Outer membrane vesicles / 遠隔臓器 / 細胞障害性 / 全身性疾患 / 肺 / 糖代謝
Outline of Research at the Start

我々は,歯周病と全身性疾患を関連づける新たな因子として,歯周病原菌が放出する『細胞外分泌小胞』を見出した。この小胞は歯周病原菌の膜によって形成,放出される小さな構造物で,小胞内部には歯周病原菌固有の病原因子や核酸を豊富に含んでいた。本研究では,『細胞外分泌小胞』が,血液などの体液を介して口腔領域外の遠隔臓器に到達するか否か,また,歯周病原菌が,菌体から細胞外分泌小胞を放出することで,自らの病原因子を広範囲に拡散し,歯周組織や全身に障害を及ぼすか調べる。さらに,『細胞外分泌小胞』内の因子が歯周病および全身性疾患の重症化の早期診断指標になりうるか検討する。

Outline of Final Research Achievements

Periodontal disease is associated with the aggravation of systemic diseases such as diabetes. We have discovered extracellular vesicles derived from periodontal pathogens as a novel factor that relates to these diseases. This study investigated the dynamics and components of extracellular vesicles derived from periodontal pathogens and their toxicity to living tissues. These extracellular secretory vesicles contain a large amount of bacterium-specific virulence factors and reach distinct organs including the liver via the blood. Extracellular vesicles that reach the liver are thought to adversely affect blood glucose levels by suppressing glucose uptake by hepatocytes. Periodontal disease is thought to be highly involved in the aggravation of systemic diseases through extracellular vesicles derived from periodontal pathogens.

Academic Significance and Societal Importance of the Research Achievements

歯周病原菌由来の細胞外分泌小胞を標識・可視化することに初めて成功し,様々な臓器に移行することを見出した。歯周病と全身性疾患の関連性における『細胞外分泌小胞』の役割を解明し,新たな学術的潮流を作り出せた。
本研究は,歯周病原菌由来の細胞外分泌小胞の内容物から歯周病と全身性疾患の病態に相関性が高い因子の同定を目指している。これらの因子は,歯周病と全身性疾患の病態を客観的に把握する分子的指標となる可能性が高い。これらの指標を用いて,歯科治療や全身性疾患の予防・治療の効果を明確に判定することが可能になると考えている。

Report

(4 results)
  • 2022 Final Research Report ( PDF )
  • 2021 Annual Research Report
  • 2020 Annual Research Report
  • 2019 Annual Research Report
  • Research Products

    (36 results)

All 2022 2021 2020 2019 Other

All Int'l Joint Research (3 results) Journal Article (13 results) (of which Int'l Joint Research: 12 results,  Peer Reviewed: 13 results,  Open Access: 7 results) Presentation (18 results) (of which Int'l Joint Research: 2 results,  Invited: 3 results) Remarks (2 results)

  • [Int'l Joint Research] 中国医科大学(中国)

    • Related Report
      2021 Annual Research Report
  • [Int'l Joint Research] 中国医科大学(中国)

    • Related Report
      2020 Annual Research Report
  • [Int'l Joint Research] 中国医科大学/哈爾浜医科大学(中国)

    • Related Report
      2019 Annual Research Report
  • [Journal Article] Outer membrane vesicles of Porphyromonas gingivalis: novel communication tool and strategy.2021

    • Author(s)
      Okamura H, Hirota K, Yoshida K, Weng Y, He Y, Shiotsu N, Uchida-Fukuhara Y, Tanai A, Guo J.
    • Journal Title

      Japanese Dental Science Review

      Volume: 57 Pages: 138-146

    • DOI

      10.1016/j.jdsr.2021.07.003

    • NAID

      120007166660

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Extracellular vesicles of P. gingivalis-infected macrophages induce lung injury.2021

    • Author(s)
      Kayo Yoshida, Kaya Yoshida, Natsumi Fujiwara, Mariko Seyama, Kisho Ono, Hotaka Kawai, Jiajie Guo, Ziyi Wang, Yao Weng, Yaqiong Yu, Yoko Uchida-Fukuhara, Mika Ikegame, Akira Sasaki, Hitoshi Nagatsuka, Hiroshi Kamioka, Hirohiko Okamura, Kazumi Ozaki
    • Journal Title

      Biochim Biophys Acta - Molecular Basis of Disease

      Volume: 1867 Issue: 11 Pages: 166236-166236

    • DOI

      10.1016/j.bbadis.2021.166236

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] O‐GlcNAcylation drives calcium signaling toward osteoblast differentiation: A bioinformatics‐oriented study2021

    • Author(s)
      Weng Yao、Wang Ziyi、Fukuhara Yoko、Tanai Airi、Ikegame Mika、Yamada Daisuke、Takarada Takeshi、Izawa Takashi、Hayano Satoru、Yoshida Kaya、Kamioka Hiroshi、Okamura Hirohiko
    • Journal Title

      BioFactors

      Volume: 47 Issue: 6 Pages: 992-1015

    • DOI

      10.1002/biof.1774

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] The role of extracellular vesicles throughout normal pregnancy and in relation to oral bacteria.2021

    • Author(s)
      Tanai A, Okamura H.
    • Journal Title

      Journal of Oral Biosciences

      Volume: 63(1) Issue: 1 Pages: 14-22

    • DOI

      10.1016/j.job.2021.01.006

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Inhibitory effect of retinoic acid receptor agoinsts on in vitro chondrogenic differentiation2020

    • Author(s)
      Sumitani Yusuke, Uchibe Kenta, Yoshida Kaya, Weng Yao, Guo Jiajie, Yuan Haoze, Ikegame Mika, Kamioka Hiroshi, Okamura Hirohiko
    • Journal Title

      Anatomical Science International

      Volume: 95 Issue: 2 Pages: 202-208

    • DOI

      10.1007/s12565-019-00512-3

    • Related Report
      2020 Annual Research Report 2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Quorum sensing molecule N-(3-oxododecanoyl)-l-homoserine lactone: An all-rounder in mammalian cell modification.2020

    • Author(s)
      Guo J, Yoshida K, Ikegame M, Okamura H.
    • Journal Title

      J Oral Biosci.

      Volume: 62(1) Issue: 1 Pages: 16-29

    • DOI

      10.1016/j.job.2020.01.001

    • Related Report
      2020 Annual Research Report 2019 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Outer membrane vesicles of Porphyromonas gingivalis attenuate insulin sensitivity by delivering gingipains to the liver.2020

    • Author(s)
      Seyama M, Yoshida K, Yoshida K, Fujiwara N, Ono K, Eguchi T, Kawai H, Guo J, Weng Y, Haoze Y, Uchibe K, Ikegame M, Sasaki A, Nagatsuka H, Okamoto K, Okamura H, Ozaki K.
    • Journal Title

      Biochim Biophys Acta Mol Basis Dis.

      Volume: 1866(6) Issue: 6 Pages: 165731-165731

    • DOI

      10.1016/j.bbadis.2020.165731

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Extracellular Vesicles Enriched with Moonlighting Metalloproteinase Are Highly Transmissive, Pro-Tumorigenic, and Trans-Activates Cellular Communication Network Factor (CCN2/CTGF): CRISPR against Cancer.2020

    • Author(s)
      Okusha Y, Eguchi T, Tran MT, Sogawa C, Yoshida K, Itagaki M, Taha EA, Ono K, Aoyama E, Okamura H, Kozaki KI, Calderwood SK, Takigawa M, Okamoto K.
    • Journal Title

      Cancers (Basel).

      Volume: 12(4). Issue: 4 Pages: 881-881

    • DOI

      10.3390/cancers12040881

    • NAID

      120006860095

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Outer membrane vesicles derived from porphylomonas gingivalis induced cell death with disruption of tight junctions in human lung epithelial cells.2020

    • Author(s)
      He Y, Shiotsu N, Uchida-Fukuhara Y, Guo J, Weng Y, Ikegame M, Wang Z, Ono K, Kamioka H, Torii Y, Sasaki A, Yoshida K, Okamura H.
    • Journal Title

      Archives of Oral Biolog

      Volume: 118 Pages: 104841-104841

    • DOI

      10.1016/j.archoralbio.2020.104841

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] N-(3-oxododecanoyl)-homoserine lactone regulates osteoblast apoptosis and differentiation by mediating intracellular calcium.2020

    • Author(s)
      Guo J, Wang Z, Weng Y, Yuan H, Yoshida K, Ikegame M, Uchibe K, Kamioka H, Ochiai K, Okamura H, Qiu L.
    • Journal Title

      Cellular Signaling

      Volume: 17 Pages: 109740-109740

    • DOI

      10.1016/j.cellsig.2020.109740

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Loading history changes the morphology and compressive force-induced expression of receptor activator of nuclear factor kappa B ligand/osteoprotegerin in MLO-Y4 osteocytes.2020

    • Author(s)
      Wang Z, Weng Y, Ishihara Y, Odagaki N, Hsu Hlaing E, Izawa T, Okamura H, Kamioka H.
    • Journal Title

      Peer J

      Volume: 8 Pages: 1-29

    • DOI

      10.7717/peerj.10244

    • NAID

      120006937507

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [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] Expression of Non-collagenous Bone Matrix Proteins in Osteoblasts Stimulated by Mechanical Stretching in the Cranial Suture of Neonatal Mice.2019

    • Author(s)
      Ikegame M, Ejiri S, Okamura H.
    • Journal Title

      J Histochem Cytochem.

      Volume: 67(2) Issue: 2 Pages: 107-116

    • DOI

      10.1369/0022155418793588

    • NAID

      120006767316

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Presentation] 間欠的・持続的伸展刺激受容後における骨芽細胞の経時的変化2022

    • Author(s)
      竹本史子,福原瑶子,池亀美華,上岡寛,岡村裕彦
    • Organizer
      第127回日本解剖学会総会・全国学術集会
    • Related Report
      2021 Annual Research Report
  • [Presentation] オホーツク文化人の歯石を対象とした古代プロテオミクス解析の検討2022

    • Author(s)
      福原瑶子,蔦谷匠,澤藤りかい,島村繁,松村博文,石田肇,池亀美華,岡村裕彦
    • Organizer
      第127回日本解剖学会総会・全国学術集会
    • Related Report
      2021 Annual Research Report
  • [Presentation] In Vitroで骨芽細胞分化を促進する一軸的伸展刺激条件の検討2021

    • Author(s)
      竹本史子,福原瑶子,池亀美華,上岡寛,岡村裕彦
    • Organizer
      第29回硬組織再生生物学会学術大会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 骨関連細胞における蛋白質脱リン酸化酵素と糖鎖修飾の役割2021

    • Author(s)
      岡村裕彦
    • Organizer
      第29回硬組織再生生物学会学術大会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] 歯周病原菌に感染したマクロファージ由来の細胞外小胞は胎盤の血管形成を阻害する2021

    • Author(s)
      棚井あいり,福原瑶子,河合穂高,江口傑徳,池亀美華,吉田賀弥,岡村裕彦
    • Organizer
      第8回日本細胞外小胞学会
    • Related Report
      2021 Annual Research Report
  • [Presentation] O-GlcNAcylation drives calcium signaling towards osteoblast differentiation2021

    • Author(s)
      Weng Yao, Heriati Sitosari, 福原瑶子,池亀美華,岡村裕彦
    • Organizer
      日本解剖学会第75回中国・四国支部学術集会
    • Related Report
      2021 Annual Research Report
  • [Presentation] O-GlcNAcylation affects the growth and migration ability of human oral squamous carcinoma cells2021

    • Author(s)
      Heriati Sitosari, Weng Yao, 福原瑶子,池亀美華,岡村裕彦
    • Organizer
      日本解剖学会第75回中国・四国支部学術集会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 骨芽細胞における転写共役因子Vgll3の役割2020

    • Author(s)
      池亀美華,岡村裕彦
    • Organizer
      第125回日本解剖学会総会・全国学術集会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Effects of maternal gut microbiome on fetal endochondral bone formation.2020

    • Author(s)
      Uchida-Fukuhara Y, Hattori T, Ikegame M, Kubota S, Okamura H
    • Organizer
      第62回歯科基礎医学会アップデートシンポジウム
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] 肺および口腔上皮細胞におけるPorphyromonas gingivalis由来の細胞外小胞の障害性2020

    • Author(s)
      山口真輝,塩津範子,竹本史子,池亀美華,吉田賀弥,上岡寛,鳥井康弘,佐々木朗,岡村裕彦
    • Organizer
      第62回歯科基礎医学会
    • Related Report
      2020 Annual Research Report
  • [Presentation] The effects of outer membrane vesicles derived from Porphyromonas gingivalis on hepatic glucose metabolisms.2019

    • Author(s)
      Kaya Yoshida, Hirohiko Okamura
    • Organizer
      Annual meeting 2019 International Society for Extracellular vesicles.
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Effect of bacterial quorum sensing factor on osteoblast differentiation and apoptosis2019

    • Author(s)
      Hirohiko Okamura, Guo jiajie
    • Organizer
      The 2nd International Conference on Bioinformatics, Biotechnology, and Biomedical Engineering
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 骨芽細胞の分化と細胞死におけるクォーラムセンシング因子AHLの影響2019

    • Author(s)
      岡村裕彦,池亀美華,吉田賀弥
    • Organizer
      第61回歯科基礎医学会学術大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 骨芽細胞におけるVgll3の発現2019

    • Author(s)
      池亀美華,内部健太,岡村裕彦
    • Organizer
      第61回歯科基礎医学会学術大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Porphyromonas gingivalis感染マクロファージの細胞外小胞が多臓器に及ぼす影響2019

    • Author(s)
      吉田賀弥,吉田佳世,尾崎和美,岡村裕彦
    • Organizer
      第6回日本細胞外小胞学会
    • Related Report
      2019 Annual Research Report
  • [Presentation] The expression and role of O-GlcNAc transferase on osteoblast and osteoclast differentiation2019

    • Author(s)
      Weng Yao, Guo Jiajie, Yuan Haoze, 吉田賀弥, 池亀美華, 岡村裕彦
    • Organizer
      日本解剖学会第74回中国・四国支部学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] The role of Vgll3 co-transcription factor during osteoblast differentiation2019

    • Author(s)
      Yuan Haoze, Mika Ikegame, Weng Yao, Guo Jiajie, Hirohiko Okamura
    • Organizer
      日本解剖学会第74回中国・四国支部学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] クォーラムセンシング因子は骨芽細胞の分化および細胞死に関与する2019

    • Author(s)
      岡村裕彦,Guo Jiajie,Weng Yao,Yuan Haoze,吉田賀弥,池亀美華
    • Organizer
      日本解剖学会第74回中国・四国支部学術集会
    • Related Report
      2019 Annual Research Report
  • [Remarks] 小さな分泌物が語る~歯周病と全身性疾患の新たな関連

    • URL

      https://www.okayama-u.ac.jp/tp/release/release_id715.html

    • Related Report
      2021 Annual Research Report
  • [Remarks] “骨が作る若返り物質”が運動で増える?!

    • URL

      https://www.okayama-u.ac.jp/tp/release/release_id583.html

    • Related Report
      2021 Annual Research Report

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Published: 2019-04-18   Modified: 2024-01-30  

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