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Integrated understanding of Del-1 functions on osteobiology and Inflammation

Research Project

Project/Area Number 17KK0165
Research Category

Fund for the Promotion of Joint International Research (Fostering Joint International Research)

Allocation TypeMulti-year Fund
Research Field Periodontology
Research InstitutionNiigata University

Principal Investigator

Maekawa Tomoki  新潟大学, 医歯学系, 研究教授 (50625168)

Project Period (FY) 2018 – 2020
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥14,430,000 (Direct Cost: ¥11,100,000、Indirect Cost: ¥3,330,000)
KeywordsDEL-1 / 骨吸収 / 骨再生 / 歯周炎 / 粘膜疾患 / 骨免疫 / 抗炎症作用 / 肺炎 / 破骨細胞 / 歯周病 / 抗炎症 / 粘膜炎 / 免疫 / 粘膜免疫 / 骨代謝 / 抗炎症物質 / 骨免疫学 / 歯周病治療学 / 骨代謝学 / Del-1 / 炎症性疾患 / トランスレーショナルリサーチ / 抗炎症分子 / 好中球
Outline of Final Research Achievements

DEL-1 is constitutively produced by osteoclasts and vascular endothelial cells, and has been found to have a variety of functions, including inhibition of osteoclasts, effects on bone metabolism and mesenchymal stem cells, and induction of regulatory T cells. It is highly possible that DEL-1 is related to the aging process, as it decreases with inflammation and aging. Studies on two mucosal diseases, periodontitis and pneumonia, have revealed the mechanism of action of DEL-1 on osteoclasts and osteoblasts and the regulation of DEL-1 expression. Collaborative research with overseas researchers who have various disease models for DEL-1 has led to a dramatic development of our research.

Academic Significance and Societal Importance of the Research Achievements

本研究成果によって,歯周炎および肺炎に対する新しい治療戦略を提示することができた.歯周炎においては,歯の周りの組織の炎症により重度な骨吸収が起き,最終的には歯が抜けてしまう.本研究で着目したDEL-1を歯周炎組織に誘導することが可能となれば,歯周炎を抑制するだけでなく,歯周炎によって失われた骨も再生可能である.さらにDEL-1による抗炎症および再生効果は,歯周炎と同様な粘膜疾患である肺炎にも応用することが可能となり,ポスト新型コロナ肺炎での破壊された肺組織の再生にDEL-1が寄与しているデータを得ることができた.今後は,DEL-1による組織再生の詳細なメカニズム解析を行い,臨床への展開を図る.

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (42 results)

All 2021 2020 2019 2018 Other

All Int'l Joint Research (1 results) Journal Article (16 results) (of which Int'l Joint Research: 13 results,  Peer Reviewed: 16 results,  Open Access: 11 results) Presentation (20 results) (of which Int'l Joint Research: 3 results,  Invited: 3 results) Book (1 results) Remarks (4 results)

  • [Int'l Joint Research] ペンシルベニア大学(米国)2019

    • Year and Date
      2019-07-06
    • Related Report
      2020 Annual Research Report
  • [Journal Article] Effects of Erythromycin on Osteoclasts and Bone Resorption via DEL-1 Induction in Mice2021

    • Author(s)
      Tamura Hikaru、Maekawa Tomoki、Domon Hisanori、Hiyoshi Takumi、Hirayama Satoru、Isono Toshihito、Sasagawa Karin、Yonezawa Daisuke、Takahashi Naoki、Oda Masataka、Maeda Takeyasu、Tabeta Koichi、Terao Yutaka
    • Journal Title

      Antibiotics

      Volume: 10 Issue: 3 Pages: 312-312

    • DOI

      10.3390/antibiotics10030312

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Analysis of Experimental Ligature-Induced Periodontitis Model in Mice2020

    • Author(s)
      Tamura Hikaru、Maekawa Tomoki、Hiyoshi Takumi、Terao Yutaka
    • Journal Title

      Methods Mol Biol

      Volume: 1 Pages: 237-250

    • DOI

      10.1007/978-1-0716-0939-2_23

    • ISBN
      9781071609385, 9781071609392
    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Erythromycin inhibits neutrophilic inflammation and mucosal disease by upregulating DEL-12020

    • Author(s)
      Maekawa Tomoki、Tamura Hikaru、Domon Hisanori、Hiyoshi Takumi、Isono Toshihito、Yonezawa Daisuke、Hayashi Naoki、Takahashi Naoki、Tabeta Koichi、Maeda Takeyasu、Oda Masataka、Ziogas Athanasios、Alexaki Vasileia Ismini、Chavakis Triantafyllos、Terao Yutaka、Hajishengallis George
    • Journal Title

      JCI Insight

      Volume: 5 Issue: 15 Pages: 136706-136706

    • DOI

      10.1172/jci.insight.136706

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] The secreted protein DEL-1 activates a β3 integrin-FAK-ERK1/2-RUNX2 pathway and promotes osteogenic differentiation and bone regeneration.2020

    • Author(s)
      Yuh DY, Maekawa T, Li X, Kajikawa T, Bdeir K, Chavakis T, Hajishengallis G.
    • Journal Title

      The Journal of Biological Chemistry

      Volume: In press Issue: 21 Pages: 7261-7273

    • DOI

      10.1074/jbc.ra120.013024

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] DHEA Inhibits Leukocyte Recruitment through Regulation of the Integrin Antagonist DEL-12020

    • Author(s)
      Ziogas Athanasios、Maekawa Tomoki、Wiessner Johannes R.、Le Thi Trang、Sprott David、Troullinaki Maria、Neuwirth Ales、Anastasopoulou Vasiliki、Grossklaus Sylvia、Chung Kyoung-Jin、Sperandio Markus、Chavakis Triantafyllos、Hajishengallis George、Alexaki Vasileia Ismini
    • Journal Title

      The Journal of Immunology

      Volume: 204 Issue: 5 Pages: 1214-1224

    • DOI

      10.4049/jimmunol.1900746

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Protective effect of hinokitiol against periodontal bone loss in ligature-induced experimental periodontitis in mice2020

    • Author(s)
      Hiyoshi Takumi、Domon Hisanori、Maekawa Tomoki、Yonezawa Daisuke、Kunitomo Eiji、Tabeta Koichi、Terao Yutaka
    • Journal Title

      Archives of Oral Biology

      Volume: 112 Pages: 104679-104679

    • DOI

      10.1016/j.archoralbio.2020.104679

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Antibacterial activity of hinokitiol against both antibiotic‐resistant and ‐susceptible pathogenic bacteria that predominate in the oral cavity and upper airways2019

    • Author(s)
      Domon Hisanori、Hiyoshi Takumi、Maekawa Tomoki、Yonezawa Daisuke、Tamura Hikaru、Kawabata Shigetada、Yanagihara Katsunori、Kimura Osamu、Kunitomo Eiji、Terao Yutaka
    • Journal Title

      Microbiology and Immunology

      Volume: 63 Issue: 6 Pages: 213-222

    • DOI

      10.1111/1348-0421.12688

    • NAID

      40021941640

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Complement-Dependent Mechanisms and Interventions in Periodontal Disease2019

    • Author(s)
      Hajishengallis G, Kajikawa T, Hajishengallis E, Maekawa T, Reis ES, Mastellos DC, Yancopoulou D, Hasturk H, Lambris JD.
    • Journal Title

      Frontiers in Immunology

      Volume: 10

    • DOI

      10.3389/fimmu.2019.00406

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Aggregatibacter actinomycetemcomitans induces detachment and death of human gingival epithelial cells and fibroblasts via elastase release following leukotoxin‐dependent neutrophil lysis2019

    • Author(s)
      Hiyoshi Takumi、Domon Hisanori、Maekawa Tomoki、Nagai Kosuke、Tamura Hikaru、Takahashi Naoki、Yonezawa Daisuke、Miyoshi Tomohiro、Yoshida Akihiro、Tabeta Koichi、Terao Yutaka
    • Journal Title

      Microbiology and Immunology

      Volume: 63 Issue: 3-4 Pages: 100-110

    • DOI

      10.1111/1348-0421.12672

    • NAID

      40021899825

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Peptides from rice endosperm protein restrain periodontal bone loss in mouse model of periodontitis2019

    • Author(s)
      Tamura Hikaru、Maekawa Tomoki、Domon Hisanori、Hiyoshi Takumi、Yonezawa Daisuke、Nagai Kosuke、Ochiai Akihito、Taniguchi Masayuki、Tabeta Koichi、Maeda Takeyasu、Terao Yutaka
    • Journal Title

      Archives of Oral Biology

      Volume: 98 Pages: 132-139

    • DOI

      10.1016/j.archoralbio.2018.11.021

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Immunization with pneumococcal elongation factor Tu enhances serotype-independent protection against Streptococcus pneumoniae infection2019

    • Author(s)
      Nagai Kosuke、Domon Hisanori、Maekawa Tomoki、Hiyoshi Takumi、Tamura Hikaru、Yonezawa Daisuke、Habuka Rie、Saitoh Akihiko、Terao Yutaka
    • Journal Title

      Vaccine

      Volume: 37 Issue: 1 Pages: 160-168

    • DOI

      10.1016/j.vaccine.2018.11.015

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Antimicrobial susceptibility of Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis clinical isolates from children with acute otitis media in Japan from 2014 to 20172019

    • Author(s)
      Nagai Kosuke、Kimura Osamu、Domon Hisanori、Maekawa Tomoki、Yonezawa Daisuke、Terao Yutaka
    • Journal Title

      Journal of Infection and Chemotherapy

      Volume: 25 Issue: 3 Pages: 229-232

    • DOI

      10.1016/j.jiac.2018.08.018

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Mechanism of Macrolide-Induced Inhibition of Pneumolysin Release Involves Impairment of Autolysin Release in Macrolide-Resistant Streptococcus pneumoniae2018

    • Author(s)
      Domon Hisanori、Maekawa Tomoki、Yonezawa Daisuke、Nagai Kosuke、Oda Masataka、Yanagihara Katsunori、Terao Yutaka
    • Journal Title

      Antimicrobial Agents and Chemotherapy

      Volume: 62 Issue: 11

    • DOI

      10.1128/aac.00161-18

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Gingival Exudatome Dynamics Implicate Inhibition of the Alternative Complement Pathway in the Protective Action of the C3 Inhibitor Cp40 in Nonhuman Primate Periodontitis2018

    • Author(s)
      Bostanci N, Bao K, Li X, Maekawa T, Grossmann J, Panse C, Briones RA, Resuello RRG, Tuplano JV, Garcia CAG, Reis ES, Lambris JD, Hajishengallis G
    • Journal Title

      Journal of Proteome Research

      Volume: 17 Issue: 9 Pages: 3153-3175

    • DOI

      10.1021/acs.jproteome.8b00263

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Neutrophil Elastase Subverts the Immune Response by Cleaving Toll-like Receptors and Cytokines in Pneumococcal Pneumonia2018

    • Author(s)
      Domon Hisanori、Nagai Kosuke、Maekawa Tomoki、Oda Masataka、Yonezawa Daisuke、Takeda Wataru、Hiyoshi Takumi、Tamura Hikaru、Yamaguchi Masaya、Kawabata Shigetada、Terao Yutaka
    • Journal Title

      Front Immunol

      Volume: 印刷中 Pages: 732-732

    • DOI

      10.3389/fimmu.2018.00732

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] A bacterial metabolite ameliorates periodontal pathogen-induced gingival epithelial barrier disruption via GPR40 signaling2018

    • Author(s)
      Yamada M, Takahashi N, Matsuda Y, Sato K, Yokoji M, Sulijaya B, Maekawa T, Ushiki T, Mikami Y, Hayatsu M, Mizutani Y, Kishino S, Ogawa J, Arita M, Tabeta K, Maeda T, Yamazaki K
    • Journal Title

      Scientific Reports

      Volume: 8 Issue: 1 Pages: 9008-9008

    • DOI

      10.1038/s41598-018-27408-y

    • NAID

      120006546008

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 歯学研究の今昔と次世代研究 DEL-1分子誘導による抗炎症および骨形成メカニズムの解明2020

    • Author(s)
      前川 知樹
    • Organizer
      第62回歯科基礎医学会学術大会,鹿児島(Web開催)
    • Related Report
      2020 Annual Research Report
  • [Presentation] マウス歯牙結紮歯周炎モデルにおけるヒノキチオールの骨吸収抑制作用の解析2020

    • Author(s)
      日吉 巧,土門久哲,前川知樹,田村 光,米澤大輔,國友栄治,寺尾 豊,多部田康一
    • Organizer
      第63回春季日本歯周病学会学術大会,郡山(Web開催)
    • Related Report
      2020 Annual Research Report
  • [Presentation] 宿主由来エラスターゼはHLAクラスII発現を抑制する2020

    • Author(s)
      土門久哲,前川知樹,寺尾 豊
    • Organizer
      第62回歯科基礎医学会学術大会,鹿児島(Web開催)
    • Related Report
      2020 Annual Research Report
  • [Presentation] ヒノキチオールの抗菌活性および抗炎症作用によるマウス歯牙結紮歯周炎モデル骨吸収抑制作用の解析2020

    • Author(s)
      日吉 巧,土門久哲,前川知樹,田村 光,國友栄治,寺尾 豊
    • Organizer
      第62回歯科基礎医学会学術大会,鹿児島(Web開催)
    • Related Report
      2020 Annual Research Report
  • [Presentation] エリスロマイシンによるDel-1誘導を介した骨代謝の制御2020

    • Author(s)
      田村 光,前川知樹,土門久哲,日吉 巧,前田健康,寺尾 豊
    • Organizer
      第62回歯科基礎医学会学術大会,鹿児島(Web開催)
    • Related Report
      2020 Annual Research Report
  • [Presentation] エリスロマイシンによるDEL-1誘導を介した破骨細胞の制御2020

    • Author(s)
      田村 光,前川知樹,土門久哲,日吉 巧,磯野俊仁,米澤大輔,前田健康,寺尾 豊,多部田康一
    • Organizer
      第63回秋季歯周病学会学術大会, 石川(Web開催)
    • Related Report
      2020 Annual Research Report
  • [Presentation] 好中球エラスターゼによる歯周炎重症化メカニズム解析2020

    • Author(s)
      日吉 巧,土門久哲, 前川知樹,田村 光,磯野俊仁,寺尾 豊,多部田康一
    • Organizer
      第63回秋季歯周病学会学術大会, 石川(Web開催)
    • Related Report
      2020 Annual Research Report
  • [Presentation] 宿主由来エラスターゼは HLA クラス II 発現を抑制する2020

    • Author(s)
      土門 久哲,前川 知樹,寺尾 豊
    • Organizer
      第63回秋季歯周病学会学術大会, 石川(Web開催)
    • Related Report
      2020 Annual Research Report
  • [Presentation] シンポジウム「オーラルエイジングを科学し全身の健康を目指す」歯周組織のアンチエイジングから歯周病を制御する2019

    • Author(s)
      前川 知樹
    • Organizer
      第19回日本抗加齢医学会総会,横浜
    • Related Report
      2019 Research-status Report
  • [Presentation] Genetic and Intervention Studies Implicating Keystone Pathogens and Del-1 as Major Targets for the Treatment of Periodontitis.2019

    • Author(s)
      Maekawa T
    • Organizer
      International Collaborative Symposium on Development of Human Resources in Practical Oral Health and Treatment
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Del-1 restrains osteoclastogenesis and inhibits inflammatory bone loss in periodontitis, rheumatoid arthritis and pneumonia of non-human primates2019

    • Author(s)
      Maekawa T
    • Organizer
      6th Symposium of the Smart-Aging Research Center, Tohoku University
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] 内因性抗炎症分子Del-1を介したマクロライド系抗菌薬の新作用機序2019

    • Author(s)
      前川知樹
    • Organizer
      第4回日本骨免疫学会ウインターセミナー,軽井沢
    • Related Report
      2018 Research-status Report
  • [Presentation] 内因性抗炎症Del-1分子による炎症性骨破壊―歯周病とリウマチ―の治療戦略2018

    • Author(s)
      前川知樹
    • Organizer
      第60回歯科基礎医学会学術大会,福岡
    • Related Report
      2018 Research-status Report
  • [Presentation] Del-1 restrains osteoclastogenesis and inhibits inflammatory bone loss in periodontitis2018

    • Author(s)
      Maekawa T
    • Organizer
      Niigata U-CU Seminar in Periodontal Research. Chulalongkorn University, Bangkok, Thailand
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] Local regulator Del1 inhibits bone-resorption via suppression of Wnt5a-Ror2 signaling2018

    • Author(s)
      Maekawa T, Domon H, Kobayashi Y, Nagai K, Yonezawa D, Terao Y, Maeda T, Hajishengallis G
    • Organizer
      96th General Session & Exhibition of the IADR, London, England
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Local regulator Del1 inhibits bone-resorption via suppression of Wnt5a-Ror2 signaling axis2018

    • Author(s)
      Maekawa T, Kobayashi Y, Domon H, Tamura H, Hiyoshi T, Maeda T, Terao Y, Hajishengallis G
    • Organizer
      ASBMR 2018 Annual Meeting, Montreal, Canada
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] 内因性抗炎症分子Del-1分子誘導による炎症性骨破壊の新規治療戦略2018

    • Author(s)
      前川知樹,小林泰浩,土門久哲,田村 光,日吉 巧,永井康介,寺尾 豊,前田健康
    • Organizer
      第4回日本骨免疫学会,沖縄
    • Related Report
      2018 Research-status Report
  • [Presentation] 内因性抗炎症Del-1分子誘導による炎症性骨破壊の新規治療戦略2018

    • Author(s)
      前川知樹
    • Organizer
      秋季日本歯周病学会学術大会,大阪
    • Related Report
      2018 Research-status Report
  • [Presentation] Keystone細菌と炎症性骨破壊制御による歯周病治療への展開2018

    • Author(s)
      前川知樹
    • Organizer
      21世紀を明るく科学する会,静岡
    • Related Report
      2018 Research-status Report
  • [Presentation] 内因性抗炎症分子Del-1を介したマクロライド系抗菌薬の新作用機序2018

    • Author(s)
      前川知樹,土門久哲,寺尾 豊
    • Organizer
      第25回マクロライド新作用研究会,東京
    • Related Report
      2018 Research-status Report
  • [Book] BIO Clinica DEL-1分子誘導による炎症性骨破壊の新規治療戦略2020

    • Author(s)
      前川 知樹
    • Total Pages
      5
    • Publisher
      北隆館
    • Related Report
      2020 Annual Research Report
  • [Remarks] 新潟大学大学院医歯学総合研究科 高度口腔機能教育研究センターホームページ

    • URL

      https://www.caos-niigata-univ.net/

    • Related Report
      2020 Annual Research Report
  • [Remarks] DEL-1を介したエリスロマイシンの抗炎症メカニズムを解明しました

    • URL

      https://www.niigata-u.ac.jp/news/2020/75897/

    • Related Report
      2020 Annual Research Report
  • [Remarks] 新潟大学医歯学総合研究科 高度口腔機能教育研究センター

    • URL

      http://www.caos-niigata-univ.net/

    • Related Report
      2019 Research-status Report
  • [Remarks] 新潟大学高度口腔機能教育研究センター

    • URL

      http://www.caos-niigata-univ.net/

    • Related Report
      2018 Research-status Report

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Published: 2018-01-25   Modified: 2022-01-27  

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