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Study of osteo-nociceptive-immune system

Research Project

Project/Area Number 15H05686
Research Category

Grant-in-Aid for Young Scientists (A)

Allocation TypeSingle-year Grants
Research Field Functional basic dentistry
Research InstitutionOsaka University

Principal Investigator

Maruyama Kenta  大阪大学, 免疫学フロンティア研究センター, 特任助教(常勤) (60724119)

Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥23,790,000 (Direct Cost: ¥18,300,000、Indirect Cost: ¥5,490,000)
Fiscal Year 2017: ¥7,800,000 (Direct Cost: ¥6,000,000、Indirect Cost: ¥1,800,000)
Fiscal Year 2016: ¥7,800,000 (Direct Cost: ¥6,000,000、Indirect Cost: ¥1,800,000)
Fiscal Year 2015: ¥8,190,000 (Direct Cost: ¥6,300,000、Indirect Cost: ¥1,890,000)
Keywords骨代謝 / 真菌感染 / 痛覚 / 炎症 / 骨髄炎 / 真菌細胞壁 / 急性疼痛 / アロディニア / ATP / 疼痛 / 感染
Outline of Final Research Achievements

It is established that nociceptor innervation occurs in skin and bone, but the mechanisms of nociceptive modulation in fungal inflammation remain unclear. In this study, we show that C. albicans stimulates Nav1.8-positive nociceptors via the β-glucan receptor Dectin-1 to induce CGRP. This induction of CGRP is independent of Bcl-10 or Malt-1 but dependent on TRPV1/TRPA1 ion channels. Hind paw β-glucan injection after Nav1.8-positive nociceptor ablation or in TRPV1/TRPA1 deficiency showed dramatically increased osteo-inflammation accompanied by impaired CGRP production. Strikingly, CGRP suppressed β-glucan-induced inflammation and osteoclast multinucleation via direct suppression of NF-κB p65 by the transcriptional repressor Jdp2 and inhibition of actin polymerization, respectively. These findings clearly suggest the role of Dectin-1-mediated sensocrine pathways in the resolution of fungal osteo-inflammation.

Report

(4 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Annual Research Report
  • 2015 Annual Research Report
  • Research Products

    (31 results)

All 2018 2017 2016 2015 Other

All Int'l Joint Research (3 results) Journal Article (11 results) (of which Int'l Joint Research: 5 results,  Peer Reviewed: 11 results,  Open Access: 7 results) Presentation (11 results) (of which Invited: 8 results) Book (1 results) Remarks (2 results) Patent(Industrial Property Rights) (3 results)

  • [Int'l Joint Research] モナコ大学ARMI(オーストラリア)

    • Related Report
      2016 Annual Research Report
  • [Int'l Joint Research]

    • Related Report
      2016 Annual Research Report
  • [Int'l Joint Research] MONASH University/ARMI(オーストラリア)

    • Related Report
      2015 Annual Research Report
  • [Journal Article] Antitumor effect of Batf2 through IL-12 p40 up-regulation in tumor-associated macrophages.2017

    • Author(s)
      Kanemaru H, Yamane F, Fukushima K, Matsuki T, Kawasaki T, Ebina I, Kuniyoshi K, Tanaka H, Maruyama K, Maeda K, Satoh T, Akira S.
    • Journal Title

      Proc Natl Acad Sci U S A

      Volume: 114 Issue: 35

    • DOI

      10.1073/pnas.1708598114

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Nociceptors Boost the Resolution of Fungal Osteoinflammation via the TRP Channel-CGRP-Jdp2 Axis2017

    • Author(s)
      Maruyama Kenta、Takayama Yasunori、Kondo Takeshi、Ishibashi Ken-ichi、Sahoo Bikash Ranjan、Kanemaru Hisashi、Kumagai Yutaro、Martino Mika?l M.、Tanaka Hiroki、Ohno Naohito、Iwakura Yoichiro、Takemura Naoki、Tominaga Makoto、Akira Shizuo
    • Journal Title

      Cell Reports

      Volume: 19 Issue: 13 Pages: 2730-2742

    • DOI

      10.1016/j.celrep.2017.06.002

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Plasmodium products persist in the bone marrow and promote chronic bone loss2017

    • Author(s)
      Lee MSJ, Maruyama K, Fujita Y, Konishi A, Lelliott PM, Itagaki S, Horii T, Lin JW, Khan SM, Kuroda E, Akira S, Ishii KJ, Coban C.
    • Journal Title

      Science Immunology

      Volume: 2 Issue: 12 Pages: 2-2

    • DOI

      10.1126/sciimmunol.aam8093

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Mechanistic and structual basis of bioengineered bovine Cathelicidin-5 with optimized therapeutic activity2017

    • Author(s)
      Bikash R. Sahoo, Kenta Maruyama, Jyotheeswara R. Edula, Takahiro Tougan, Yuxi Lin, Young-Ho Lee, Toshihiro Horii, and Toshimichi Fujiwara
    • Journal Title

      Scientific Reports

      Volume: 7:44781 Issue: 1 Pages: 44781-44796

    • DOI

      10.1038/srep44781

    • Related Report
      2017 Annual Research Report 2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Netrins as Prophylactic Targets of Skeletal diseases: A Double-Edged Sword?2017

    • Author(s)
      *Kenta Maruyama, Naoki Takemura, Mikael M. Martino, Takeshi Kondo, and Shizuo Akira.
    • Journal Title

      Pharmacological Research

      Volume: 122 Pages: 46-52

    • DOI

      10.1016/j.phrs.2017.05.011

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Bone-protective Functions of Netrin 1 Protein2016

    • Author(s)
      Kenta Maruyama, Takahiko Kawasaki, Masahide Hamaguchi, Motomu Hashimoto, Moritoshi Furu, Hiromu Ito, Takao Fujii, Naoki Takemura, Thangaraj Karuppuchamy, Takeshi Kondo, Takumi Kawasaki, Masahiro Fukusaka, Takuma Misawa, Tatsuya Saitoh, Yutaka Suzuki, Mikael M Martino, Yutaro Kumagai, and Shizuo Akira
    • Journal Title

      Journal of Biological Chemistry

      Volume: 291 Issue: 46 Pages: 23854-23868

    • DOI

      10.1074/jbc.m116.738518

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 5-azacytidine-induced protein 2 (AZI2) regulates bone mass by fine-tuning osteoclast survival.2015

    • Author(s)
      Maruyama K, Fukasaka M, Uematsu S, Takeuchi O, Kondo T, Saitoh T, Martino M, Akira S.
    • Journal Title

      J Biol Chem

      Volume: 290 Issue: 15 Pages: 9377-9386

    • DOI

      10.1074/jbc.m114.631374

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Extracellular matrix-inspired growth factor delivery systems for bone regeneration.2015

    • Author(s)
      Mikael M. Marutino, Priscilla S. Briquez, Kenta Maruyama, and Jeffrey A. Hubbell
    • Journal Title

      Advanced Drug Delivery Reviews

      Volume: 94 Pages: 41-54

    • DOI

      10.1016/j.addr.2015.04.007

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Emerging molecules in the interface between skeletal system and innate immunity.2015

    • Author(s)
      Kenta Maruyama* and Shizuo Akira* (*corresponding author)
    • Journal Title

      Pharmacological Research

      Volume: 99 Pages: 223-228

    • DOI

      10.1016/j.phrs.2015.06.005

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Osteoprotegerin Regulates Pancreatic β-Cell Homeostasis upon Microbial Invasion.2015

    • Author(s)
      Yukiko Kuroda, Kenta Maruyama, Hideki Fujii, Isamu Sugawara, Shigeru Ko, Hisataka Yasuda, Hidenori Matsui, and Koichi Matsuo
    • Journal Title

      PLoS One

      Volume: 11 Issue: 1 Pages: e0146544-e0146544

    • DOI

      10.1371/journal.pone.0146544

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Inhibition of IL-1R1/MyD88 signalling promotes mesenchymal stem cell-driven tissue regeneration.2015

    • Author(s)
      Mikael M Martino, Kenta Maruyama, Scott Stanger, Takashi Satoh, Osamu Takeuchi, Ralph Muller, and Shizuo Akira
    • Journal Title

      Nature Communications

      Volume: 7 Issue: 1 Pages: 11051-11051

    • DOI

      10.1038/ncomms11051

    • NAID

      120005743659

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] 真菌感染随伴症状とATP2018

    • Author(s)
      丸山健太
    • Organizer
      第138回 日本薬学会 一般シンポジウム“次世代のプリン作動性化学伝達遮断薬の創成を目指して
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] 革新的組織滞留型抗炎症骨保護ペプチド2017

    • Author(s)
      丸山健太
    • Organizer
      メディカルジャパン2017大阪
    • Place of Presentation
      インテックス大阪、大阪
    • Year and Date
      2017-02-17
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] 骨神経免疫トライアングル理論を基盤とした真菌感染随伴疼痛の発生機構ならびにその生物学的意義に関する一考察2017

    • Author(s)
      丸山健太
    • Organizer
      生理学研究所研究会 痛みの理解を目指した先端的アプローチ
    • Place of Presentation
      自然科学研究機構岡崎カンファレンスセンター、名古屋
    • Year and Date
      2017-01-30
    • Related Report
      2016 Annual Research Report
  • [Presentation] Dectin-1-stimulated Sensocrine Nociceptor Pathways Inhibit Fungal Osteo-inflammation2017

    • Author(s)
      Kenta Maruyama
    • Organizer
      第19回 武田科学振興財団生命科学シンポジウム
    • Place of Presentation
      武田薬品研修所、大阪
    • Year and Date
      2017-01-20
    • Related Report
      2016 Annual Research Report
  • [Presentation] 真菌感染随伴疼痛の生物学的意義とは?2017

    • Author(s)
      丸山健太
    • Organizer
      第59回 歯科基礎医学会学術大会アップデートシンポジウム
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] New players in Osteo-innate-immune system and their unexpected roles; novel molecules for novel therapies2016

    • Author(s)
      Kenta Maruyama
    • Organizer
      Monash University Special Seminar
    • Place of Presentation
      Monash University, ARMI (Clayton, Australia)
    • Year and Date
      2016-11-30
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] 骨神経免疫トライアングル理論を基盤とした真菌感染症の再考2016

    • Author(s)
      丸山健太、石橋健一、大野尚仁
    • Organizer
      第60回日本医真菌学会総会・学術集会
    • Place of Presentation
      台東館、東京
    • Year and Date
      2016-10-01
    • Related Report
      2016 Annual Research Report
  • [Presentation] 革新的局所滞留型抗炎症性骨保護ペプチド2016

    • Author(s)
      丸山健太
    • Organizer
      科学技術振興機構 大阪大学新技術説明会
    • Place of Presentation
      JST東京本部別館1F、東京
    • Year and Date
      2016-07-21
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] Novel prophylactic targets of osteoporosis and pain: from Neuro-osteological point of view2016

    • Author(s)
      Kenta Maruyama
    • Organizer
      千里ライフサイエンス財団 SENRIの会
    • Place of Presentation
      千里ライフサイエンスセンター
    • Year and Date
      2016-01-13
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] Identification of the osteoclast fusion inhibitor2015

    • Author(s)
      Kenta Maruyama
    • Organizer
      アステラス病態代謝研究会
    • Place of Presentation
      東京工業倶楽部
    • Year and Date
      2015-10-17
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] New players in skeletal system and their unexpected roles: novel molecules for novel therapies2015

    • Author(s)
      Kenta Maruyama
    • Organizer
      日本骨代謝学会
    • Place of Presentation
      京王プラザホテル
    • Year and Date
      2015-06-25
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Book] 実験医学 2017年12月号 Vol.35 No.19、「Type2サイトカインによる感覚神経の直接刺激が痒みを増悪させる」2017

    • Author(s)
      丸山健太
    • Total Pages
      137
    • Publisher
      羊土社
    • ISBN
      9784758125024
    • Related Report
      2017 Annual Research Report
  • [Remarks]

    • URL

      http://researchmap.jp/read0133961/?lang=english

    • Related Report
      2016 Annual Research Report
  • [Remarks]

    • URL

      http://researchmap.jp/read0133961/

    • Related Report
      2015 Annual Research Report
  • [Patent(Industrial Property Rights)] 真菌感染における宿主応答抑制剤2017

    • Inventor(s)
      丸山健太、森山芳則、野村政壽
    • Industrial Property Rights Holder
      丸山健太、森山芳則、野村政壽
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2017-134071
    • Filing Date
      2017
    • Related Report
      2017 Annual Research Report
  • [Patent(Industrial Property Rights)] 組織損傷治療剤2017

    • Inventor(s)
      丸山健太、マルティーノ ミカエル エム、審良静男
    • Industrial Property Rights Holder
      丸山健太、マルティーノ ミカエル エム、審良静男
    • Industrial Property Rights Type
      特許
    • Filing Date
      2017-02-24
    • Related Report
      2016 Annual Research Report
  • [Patent(Industrial Property Rights)] 組織損傷治療剤2016

    • Inventor(s)
      丸山健太、ミカエルマルティーノエム、審良静男
    • Industrial Property Rights Holder
      丸山健太、ミカエルマルティーノエム、審良静男
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2016-036869
    • Filing Date
      2016-03-16
    • Related Report
      2015 Annual Research Report

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Published: 2015-04-16   Modified: 2019-10-18  

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