Morphometrical and quantitative transcriptome analyses of C-C chemokine receptor 5 in functional structure of osteoclasts
Project/Area Number |
16K20412
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Research Category |
Grant-in-Aid for Young Scientists (B)
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Allocation Type | Multi-year Fund |
Research Field |
Morphological basic dentistry
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Research Institution | Ehime 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)
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Research Collaborator |
Iimura Tadahiro
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Project Period (FY) |
2016-04-01 – 2019-03-31
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Project Status |
Completed (Fiscal Year 2018)
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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)
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Keywords | osteoclast / 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.
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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。
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Report
(4 results)
Research Products
(30 results)
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[Journal Article] PV1, a novel Plasmodium falciparum merozoite dense granule protein, interacts with exported protein in infected erythrocytes.2018
Author(s)
Morita M, Nagaoka H, Ntege E, Kanoi B, Ito D, Nalata T, Lee JW, Tokunaga T, Torii M, Tsuboi T, Takashima E.
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Journal Title
Scientific Reports
Volume: 8
Pages: 3696
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Uhrf1 is indispensable for normal limb growth by regulating chondrocyte differentiation through specific gene expression.2018
Author(s)
Yamashita M, Inoue K, Saeki N, Ideta-Otsuka M, Yanagihara Y, Sawada Y, Sakakibara I, Lee JW, Ichikawa K, Kamei Y, Iimura T, Imai Y.
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Journal Title
Development
Volume: 145
Pages: 157412
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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[Journal Article] Bone Research2017
Author(s)
Aya Tanaka, Ji-Won Lee, Kyoko Hirano, Yukihiro Isogai, Toshinori Ishizuya, Rhoko Takao-Kawabata, Tadahiro Iimura
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Journal Title
Administration frequency as well as dosage of PTH are associated with development of cortical porosity in ovariwctomized rats
Volume: 5
Pages: -
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
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[Journal Article] PLOS One2017
Author(s)
Hiroshi Yamane, Aya Takakura, Yukari Shimadzu, Toshiyuki Kodama, Ji-Won Lee, Yukihiro Isogai, Toshinori Ishizuya Rhoko Takao-Kawabata, Tadahiro Iimura
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Journal Title
Acute development of cortical porosity and endosteal naive bone formation from the daily but not weekly short-term administration of PTH in rabbit
Volume: -
Pages: -
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Journal of Oral Biosciences2017
Author(s)
Tadahiro Iimura, Ji-Won Lee
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Journal Title
Unveiling a rhythmic regulatory mode hidden in developmental tissue growth by fluorescence live imaging-based mathematical modeling
Volume: 59
Pages: 6-11
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
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[Journal Article] Japanse Dental Science Review2017
Author(s)
Ji-Won Lee, Tadahiro Iimura
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Journal Title
Shedding quantitative fluorescence light on novel regulatory mechanisms in skeletal biomedicine and biodentistry
Volume: 53
Pages: 2-10
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
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[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 – 2016-05-17
Related Report
Int'l Joint Research