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Morphometrical and quantitative transcriptome analyses of C-C chemokine receptor 5 in functional structure of osteoclasts

Research Project

Project/Area Number 16K20412
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Morphological basic dentistry
Research InstitutionEhime University

Principal Investigator

LEE JIWON  愛媛大学, プロテオサイエンスセンター, 助教(特定教員) (70711274)

Research Collaborator Iimura Tadahiro  
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywordsosteoclast / osteoblast / chemokine receptor 5 / bone metabolism / chemokine / bone / CCR5 / RANKL / chemokine receptor / RNA-sequence / histomorphometry
Outline of Final Research Achievements

This study demonstrated that the blockade of CCR5 using its specific antibodies impaired in vitro human osteoclastogenesis with disorganized actin rings, but not osteoblastogenesis. Ccr5-deficient mice with dysfunctional osteoclasts were resistant to osteoporotic stimulation via the administration of receptor activator of nuclear factor kappa-B ligand (RANKL), which induces osteoporosis independently of the inflammatory and immunomodulatory responses. Furthermore, CCL5, a ligand for CCR5, enhanced the integrin- and chemokine-mediated pathways in osteoclast. The present study experimentally provides further evidence that CCR5 plays an essential role in bone destructive diseases through the functional regulation of osteoclasts, thus suggesting a skeletal benefit of the CCR5-targeting therapy.

Academic Significance and Societal Importance of the Research Achievements

HIV感染治療薬の標的分子であるCCR5が骨の代謝も調節していることを解明した。抗CCR5治療薬はHIV感染患者の延命に大きく貢献しますが、高齢化に伴う運動器疾患への影響が懸念されていた。今回の研究でCCR5が骨を吸収する破骨細胞にも存在し、CCR5の機能抑制は破骨細胞の骨吸収能を抑えることを解明した。さらに、動物実験では、CCR5の機能抑制が骨粗鬆症を抑えることを発見された。これらの実験観察は、抗CCR5治療薬はHIV感染症のみならず、骨粗鬆症を始めとする骨吸収性疾患に対してもメリットをもたらす可能性を明らかにした。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (27 results)

All 2018 2017 2016

All Journal Article (11 results) (of which Int'l Joint Research: 9 results,  Peer Reviewed: 11 results,  Open Access: 9 results,  Acknowledgement Compliant: 4 results) Presentation (16 results) (of which Int'l Joint Research: 5 results,  Invited: 8 results)

  • [Journal Article] PV1, a novel Plasmodium falciparum merozoite dense granule protein, interacts with exported protein in infected erythrocytes2018

    • Author(s)
      Morita Masayuki、Nagaoka Hikaru、Ntege Edward H.、Kanoi Bernard N.、Ito Daisuke、Nakata Takahiro、Lee Ji-Won、Tokunaga Kazuaki、Iimura Tadahiro、Torii Motomi、Tsuboi Takafumi、Takashima Eizo
    • Journal Title

      Scientific Reports

      Volume: 8 Issue: 1 Pages: 3696-3696

    • DOI

      10.1038/s41598-018-22026-0

    • Related Report
      2018 Annual Research Report 2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Harmine promotes molar root development via SMAD1/5/8 phosphorylation.2018

    • Author(s)
      Fujiwara N, Lee JW, Kumakami-Sakano M, Otsu K, Woo JT, Iseki S, Ota
    • Journal Title

      Biochem Biophys Res Commun.

      Volume: 497 Issue: 3 Pages: 924-929

    • DOI

      10.1016/j.bbrc.2017.12.062

    • Related Report
      2018 Annual Research Report 2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] 骨組織の顕微鏡研究2018

    • Author(s)
      飯村 忠浩、李 智媛
    • Journal Title

      顕微鏡

      Volume: 23 Pages: 24-28

    • NAID

      130007686936

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] テリパラチドの高頻度投与は皮質骨空隙形成を誘導する2018

    • Author(s)
      高倉 綾、李 智媛、 山根 宏志、高尾 亮子、飯村 忠浩
    • Journal Title

      日本骨形態計測学会雑誌

      Volume: 28 Pages: 31-37

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Uhrf1 is indispensable for normal limb growth by regulating chondrocyte differentiation through specific gene expression2017

    • Author(s)
      Yamashita Michiko、Inoue Kazuki、Saeki Noritaka、Ideta-Otsuka Maky、Yanagihara Yuta、Sawada Yuichiro、Sakakibara Iori、Lee Jiwon、Ichikawa Koichi、Kamei Yoshiaki、Iimura Tadahiro、Igarashi Katsuhide、Takada Yasutsugu、Imai Yuuki
    • Journal Title

      Development

      Volume: 145 Issue: 1 Pages: 157412-157412

    • DOI

      10.1242/dev.157412

    • Related Report
      2018 Annual Research Report 2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] The HIV co-receptor CCR5 regulates osteoclast function.2017

    • Author(s)
      Lee JW, Hoshino A, Inoue K, Saitou T, Uehara S, Kobayashi Y, Ueha S, Matsushima K, Yamaguchi A, Imai Y, Iimura T.
    • Journal Title

      Nat Commun

      Volume: 8 Issue: 1 Pages: 2226-2226

    • DOI

      10.1038/s41467-017-02368-5

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Bone Research2017

    • Author(s)
      Aya Tanaka, Ji-Won Lee, Kyoko Hirano, Yukihiro Isogai, Toshinori Ishizuya, Rhoko Takao-Kawabata, Tadahiro Iimura
    • Journal Title

      Administration frequency as well as dosage of PTH are associated with development of cortical porosity in ovariwctomized rats

      Volume: 5 Issue: 1 Pages: 17002-17002

    • DOI

      10.1038/boneres.2017.2

    • Related Report
      2017 Research-status Report 2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Acute development of cortical porosity and endosteal naive bone formation from the daily but not weekly short-term administration of PTH in rabbit.2017

    • Author(s)
      Yamane H, Takakura A, Shimadzu Y, Kodama T, Lee JW, Isogai Y, Ishizuya T, Takao-Kawabata R, Iimura T.
    • Journal Title

      PLoS One.

      Volume: 12 Issue: 4 Pages: e0175329-e0175329

    • DOI

      10.1371/journal.pone.0175329

    • Related Report
      2017 Research-status Report 2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Journal of Oral Biosciences2017

    • Author(s)
      Tadahiro Iimura, Ji-Won Lee
    • Journal Title

      Unveiling a rhythmic regulatory mode hidden in developmental tissue growth by fluorescence live imaging-based mathematical modeling

      Volume: 59 Issue: 1 Pages: 6-11

    • DOI

      10.1016/j.job.2016.09.001

    • Related Report
      2017 Research-status Report 2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Shedding quantitative fluorescence light on novel regulatory mechanisms in skeletal biomedicine and biodentistry.2017

    • Author(s)
      Lee JW, Iimura T
    • Journal Title

      Japanese of Dental Science Review

      Volume: 53 Issue: 1 Pages: 2-10

    • DOI

      10.1016/j.jdsr.2016.04.005

    • NAID

      50012041274

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Japanse Dental Science Review2017

    • Author(s)
      Ji-Won Lee, Tadahiro Iimura
    • Journal Title

      Shedding quantitative fluorescence light on novel regulatory mechanisms in skeletal biomedicine and biodentistry

      Volume: 53 Pages: 2-10

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Presentation] HIV, co-receptor, CCR5 plays an essential role in bone-destructive conditions through the functional regulation of osteoclast2018

    • Author(s)
      Lee JW
    • Organizer
      The 36th annual meeting of the Japanese society for bone and mineral research
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] CCR5, a therapeutic target of HIV infection, is required for osteoclast differentiation and function, suggesting a skeletal merit of the CCR5 targeting HIV therapy.2018

    • Author(s)
      Lee JW
    • Organizer
      BioForum@Dental School, Okayama University
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] The HIV co-receptor CCR5 regulates cellular pathways required for osteoclast function2018

    • Author(s)
      Lee JW
    • Organizer
      The 370th Matsumoto University
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] CCR5 is required for osteoclast function through regulating lysosomal vesicle trafficking2018

    • Author(s)
      LEe JW, Iami Y, Iimura T
    • Organizer
      Annual meeting of American Society for Bone and Mineral Research, Montreal, Canada
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] The HIV co-receptor CCR5 regulates cellular pathways required for osteoclast function2018

    • Author(s)
      Lee JW
    • Organizer
      第3回日本骨免疫学会ウィンターセミナー
    • Related Report
      2017 Research-status Report
  • [Presentation] Requirement of CCR5, a co-receptor of HIV, for the functional cellular architecture of osteoclasts, providing experimental evidences for the direct association between loss of CCR5 and resistance to bone loss2017

    • Author(s)
      Lee JW, Inoue K, Uehara S, Kobayashi Y, Imai Y, Iimura T
    • Organizer
      Australian and New Zealand Bone and Mineral Society
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] Novel regulatory mechanisms of osteoclast function, as revealed by combinatorial approaches of functional live-imaging and molecular omics2017

    • Author(s)
      Lee JW
    • Organizer
      The 39th Annual meeting of the molecular biology society of Japan
    • Related Report
      2017 Research-status Report
  • [Presentation] HIV治療薬標的分子CCR5の破骨細胞機能分化における必須の機能-CCR5を標的としたHIV治療は骨吸収性疾患に対してもメリットをもたらす可能性がある-2017

    • Author(s)
      李 智媛、飯村 忠浩
    • Organizer
      第35回日本骨代謝学会
    • Related Report
      2017 Research-status Report
  • [Presentation] Novel regulatory mechanisms of osteoclast function, as revealed by combinatorial approaches of functional live-imaging and molecular comics2016

    • Author(s)
      Ji-Won Lee
    • Organizer
      39th Annual Meeting of the Molecular Biology Society of Japan
    • Place of Presentation
      横浜、日本
    • Year and Date
      2016-11-30
    • Related Report
      2016 Research-status Report
    • Invited
  • [Presentation] C-C chemokine receptor 5, a co-receptor of HIV, -mediated signal is required for architectural function of osteoclasts, thus for RANKL-induced bone destruction2016

    • Author(s)
      Ji-Won Lee, Akiyoshi Hoshino, Yasuhiro Kobayashi, Shunsuke Uehara, Yuuki Imai, Tadahiro Iimura
    • Organizer
      1st Skeletal Science Retreat
    • Place of Presentation
      熱海、日本
    • Year and Date
      2016-11-26
    • Related Report
      2016 Research-status Report
  • [Presentation] Essential roles of C-C chemokine-mediated signaling in mature osteoclast function2016

    • Author(s)
      Ji-Won Lee, Akiyoshi Hoshino, Yasuhiro Kobayashi, Shunsuke Uehara, Yuuki Imai, Tadahiro Iimura
    • Organizer
      6th Asia-Pacific Osteoporosis Meeting
    • Place of Presentation
      Signapore
    • Year and Date
      2016-11-04
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] 機能的生細胞イメージングとオミックス解析による破骨細胞調節機能の解明2016

    • Author(s)
      Ji-Won Lee
    • Organizer
      58th 歯科基礎医学会学術大会
    • Place of Presentation
      札幌、日本
    • Year and Date
      2016-08-24
    • Related Report
      2016 Research-status Report
    • Invited
  • [Presentation] Role of chemokine-mediated signaling in architectural function of osteoclasts2016

    • Author(s)
      Ji-Won Lee
    • Organizer
      34th 日本骨代謝学会
    • Place of Presentation
      大阪、日本
    • Year and Date
      2016-07-21
    • Related Report
      2016 Research-status Report
    • Invited
  • [Presentation] C-C chemokine receptor 5, a co-receptor of HIV, -mediated signal is required for geometric architecture and function of osteoclasts, thus for RANKL-induced bone destruction2016

    • Author(s)
      Ji-Won Lee, Akiyoshi Hoshino, Kazuki Inoue, Shunsuke Uehara, Yasuhiro Kobayashi, Satoshi Ueha, Kouji Matsushima, Akira Yamaguchi, Yuuki Imai, Tadahiro Iimura
    • Organizer
      43rd Annual European Calcified Tissue Society Congress
    • Place of Presentation
      Rome, Italy
    • Year and Date
      2016-05-14
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] Essential role of C-C chemokine-mediated signaling in mature osteoclast function2016

    • Author(s)
      Ji-Won Lee
    • Organizer
      7th 骨バイオサイエンス研究会
    • Place of Presentation
      岡山、日本
    • Related Report
      2016 Research-status Report
    • Invited
  • [Presentation] Unveiling novel regulatory mechanisms of osteoclasts by integrative approaches of bio-imaging and molecular comics2016

    • Author(s)
      Ji-Won Lee
    • Organizer
      Protein Island Matsuyama (PIM) International symposium 2016
    • Place of Presentation
      松山、日本
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research / Invited

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Published: 2016-04-21   Modified: 2023-03-23  

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