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Intravital imaging of bone cell physiology and bone-resident cancers

Planned Research

Project AreaMutli-dimensional fluorescence live imaging of cellular function and molecular activity
Project/Area Number 22113007
Research Category

Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)

Allocation TypeSingle-year Grants
Review Section Biological Sciences
Research InstitutionOsaka University

Principal Investigator

ISHII Masaru  大阪大学, 生命機能研究科, 教授 (10324758)

Project Period (FY) 2010-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥109,850,000 (Direct Cost: ¥84,500,000、Indirect Cost: ¥25,350,000)
Fiscal Year 2014: ¥16,380,000 (Direct Cost: ¥12,600,000、Indirect Cost: ¥3,780,000)
Fiscal Year 2013: ¥17,290,000 (Direct Cost: ¥13,300,000、Indirect Cost: ¥3,990,000)
Fiscal Year 2012: ¥18,070,000 (Direct Cost: ¥13,900,000、Indirect Cost: ¥4,170,000)
Fiscal Year 2011: ¥17,940,000 (Direct Cost: ¥13,800,000、Indirect Cost: ¥4,140,000)
Fiscal Year 2010: ¥40,170,000 (Direct Cost: ¥30,900,000、Indirect Cost: ¥9,270,000)
Keywords細胞動態 / 骨髄 / 破骨細胞 / がん細胞 / イメージング / 骨髄環境 / ケモカイン / がん幹細胞 / 細胞分化 / ニッチ
Outline of Final Research Achievements

During the last decade, multi-photon fluorescent microscopy has launched a new era. By using this advanced imaging technique in this study we have established a new system for visualizing in situ behavior of a diversity of living cells within intact tissues and organs. Among them, we succeeded in visualizing the various dynamic phenomena within bones, a mysterious organ where various kinds of hematopoietic and immune cells are produced and functioning although poorly analyzed by conventional methodology such as histological analyses with decalcified bones. Especially we have focused on the behavior of osteoclast, a kind of specialized macrophage contributing to physiological bone remodeling as well as to bone destruction in cancer metastasis. In this study we have revealed novel mechanisms controlling migration and function of different bone cells in situ and also propose the further applications of this novel methodology in bone and cancer biology.

Report

(6 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Annual Research Report
  • 2012 Annual Research Report
  • 2011 Annual Research Report
  • 2010 Annual Research Report
  • Research Products

    (30 results)

All 2015 2014 2013 2012 2011 2010 Other

All Journal Article (16 results) (of which Peer Reviewed: 16 results,  Open Access: 3 results,  Acknowledgement Compliant: 5 results) Presentation (8 results) (of which Invited: 6 results) Remarks (4 results) Patent(Industrial Property Rights) (2 results) (of which Overseas: 1 results)

  • [Journal Article] Visualized macrophage dynamics and significance of S100A8 in obese fat.2015

    • Author(s)
      Sekimoto et al.
    • Journal Title

      Proc Natl Acad Sci USA

      Volume: ePub Issue: 16

    • DOI

      10.1073/pnas.1409480112

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Intravital bone imaging by two-photon excitation microscopy to identify osteocytic osteolysis in vivo.2015

    • Author(s)
      Sano et al.
    • Journal Title

      Bone

      Volume: 74 Pages: 134-139

    • DOI

      10.1016/j.bone.2015.01.013

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Dnmt3a regulates osteoclast differentiation by coupling to an S-adenosyl methionine-producing metabolic pathway.2015

    • Author(s)
      Nishikawa et al.
    • Journal Title

      Nature Medicine

      Volume: 21 Issue: 3 Pages: 281-287

    • DOI

      10.1038/nm.3774

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] RFPL4A increases the G1 population and decreases sensitivity to chemotherapy in human colorectal cancer cells.2015

    • Author(s)
      Naito et al.
    • Journal Title

      J Biol Chem

      Volume: 290 Issue: 10 Pages: 6326-6337

    • DOI

      10.1074/jbc.m114.614859

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Interferon-α acts on the S/G2/M phases to induce apoptosis in the G1 phase of an IFNAR2-expressing hepatocellular carcinoma cell line.2014

    • Author(s)
      Maeda et al.
    • Journal Title

      J Biol Chem

      Volume: 289 Issue: 34 Pages: 23786-23795

    • DOI

      10.1074/jbc.m114.551879

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Cell cycle-dependent Rho GTPase activity dynamically regulates cancer cell motility and invasion in vivo.2014

    • Author(s)
      Kagawa Y, Matsumoto S, Kamioka Y, Mimori M, Naito Y, Ishii T, Okuzaki D, Nishida N, Maeda S, Naito A, Kikuta J, Nishikawa K, Nishimura J, Haraguchi N, Takemasa I, Mizushima T, Ikeda M, Yamamoto H, Sekimoto M, Ishii H, Doki Y, Matsuda M, Kikuchi A, Mori M, Ishii M
    • Journal Title

      PLoS One

      Volume: 8 Issue: 12 Pages: e83629-e83629

    • DOI

      10.1371/journal.pone.0083629

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Dynamic visualization of RANKL and Thl7-mediated osteoclast function.2013

    • Author(s)
      菊田 順一
    • Journal Title

      The journal of Clinical Investigation

      Volume: vol.123 Pages: 866-873

    • DOI

      10.1172/jci65054

    • Related Report
      2013 Annual Research Report 2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] S1P-mediated osteoclast precursor monocyte migration is a critical point of control in antibone-resorptive action of active vitamin D.2013

    • Author(s)
      Kikuta J, Kawamura S, Okiji F, Shirazaki M, Sakai S, Saito H, Ishii M
    • Journal Title

      Proc. Natl. Acad. Sci. USA

      Volume: 110 Pages: 7009-7013

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Sphingosine- 1-phosphate-mediated osteoclast precursor monocyte migration is a critical point of control in antibone-resorptive action of active vitamin D.2013

    • Author(s)
      菊田 順一
    • Journal Title

      Proceedings of the National Academy of Sciences of the United States of America

      Volume: vol. 110 Issue: 17 Pages: 7009-7013

    • DOI

      10.1073/pnas.1218799110

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Recent advances in intravital imaging of dynamic biological systems.2012

    • Author(s)
      菊田 順一
    • Journal Title

      Journal of Pharmacological Sciences

      Volume: vol.119 Issue: 2 Pages: 193-197

    • DOI

      10.4049/jimmunol.1201345

    • NAID

      10030986703

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The sphingosine-1-phosphate transporter Spns2 expressed on endothelial cells regulates lymphocyte trafficking in mice2012

    • Author(s)
      Fukuhara S, et al
    • Journal Title

      J Clin Invest

      Volume: (In press)(未定) Issue: 4 Pages: 1416-1426

    • DOI

      10.1172/jci60746

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] In Vivo Fluorescence Imaging of Bone-Resorbing Osteoclasts2011

    • Author(s)
      T. Kowada, J. Kikuta, A. Kubo, M. Ishii, H. Maeda, S. Mizukami & K. Kikuchi
    • Journal Title

      J. Am. Chem. Soc

      Volume: 133 Issue: 44 Pages: 17772-17776

    • DOI

      10.1021/ja2064582

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] S1P-targeted therapy for elderly rheumatoid arthritis patients with osteoporosis2011

    • Author(s)
      Kikuta, et al
    • Journal Title

      Rheumatol.Int.

      Volume: 31 Issue: 7 Pages: 967-969

    • DOI

      10.1007/s00296-010-1634-8

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] S1P-targeted therapy for elderly rheumatoid arthritis patients with osteoporosis.2011

    • Author(s)
      Kikuta, Ishii, et al.
    • Journal Title

      Rheumatology International

      Volume: (in press)

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The role of sphingosine 1-phosphate in migration of osteoclast precursors ; an application of intravital two-photon microscopy.2011

    • Author(s)
      Ishii, et al.
    • Journal Title

      Molecule and Cells

      Volume: (in press)

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Chemorepulsion by blood S1P regulates osteoclast precursor mobilization and bone remodeling in vivo.2010

    • Author(s)
      Ishii, et al.
    • Journal Title

      Journal of Experimental Medicine

      Volume: 207 Pages: 2793-2798

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Presentation] Intravital multiphoton imaging revealing immune cell dynamics in inflammation and bone destruction in vivo.2014

    • Author(s)
      Masaru Ishii
    • Organizer
      Japan-Germany Cancer Workshop
    • Place of Presentation
      Berlin, Germany
    • Year and Date
      2014-11-14 – 2014-11-15
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] Intravital multiphoton imaging revealing immune cell dynamics in bone destruction in vivo.2014

    • Author(s)
      Masaru Ishii
    • Organizer
      CSHA Conference on Bone and Cartilage: from Development to Human Diseases
    • Place of Presentation
      Suzhou, China
    • Year and Date
      2014-11-04 – 2014-11-07
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] S1P-mediated control of bone cell dynamics visualized by intra-vital microscopy2014

    • Author(s)
      Masaru Ishii
    • Organizer
      Gordon Research Conference
    • Place of Presentation
      Ventura, CA (USA)
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] Intravital multiphoton imaging dissecting cellular dynamics in live animals.2013

    • Author(s)
      Masaru Ishii
    • Organizer
      Cold Spring Harbor Conference Asia
    • Place of Presentation
      Suzhou (China)
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] Dynamic behaviors of osteoclast function visualized by intravital imaging2012

    • Author(s)
      Masaru Ishii
    • Organizer
      Cold Spring Harbor Asia Conference
    • Place of Presentation
      Suzhou, China
    • Year and Date
      2012-06-11
    • Related Report
      2012 Annual Research Report
    • Invited
  • [Presentation] Roles of S1P in osteoclast regulation and bone physiology.2012

    • Author(s)
      Masaru Ishii
    • Organizer
      2012 Gordon Research Conference
    • Place of Presentation
      Il Ciocco, Italy
    • Year and Date
      2012-04-22
    • Related Report
      2012 Annual Research Report
    • Invited
  • [Presentation] Roles of S1P in osteoclast regulation and bone remodeling2011

    • Author(s)
      Masaru Ishii
    • Organizer
      2011 FASEB Summer Research Conference
    • Place of Presentation
      Il Ciocco, Italy(招待講演)
    • Year and Date
      2011-08-18
    • Related Report
      2011 Annual Research Report
  • [Presentation] Chemokine-mediated migration control of osteoclast precursors visualized by live bone imaging2010

    • Author(s)
      Masaru Ishii
    • Organizer
      3rd International Conference of Osteoimmunology
    • Place of Presentation
      Santorini/Greece(招待講演)
    • Year and Date
      2010-06-21
    • Related Report
      2010 Annual Research Report
  • [Remarks] 大阪大学大学院医学系研究科/生命機能研究科免疫細胞生物学教室

    • URL

      http://www.icb.med.osaka-u.ac.jp/

    • Related Report
      2014 Annual Research Report
  • [Remarks] 大阪大学医学系研究科生命機能研究科免疫細胞生物学教室

    • URL

      http://www.icb.med.osaka-u.ac.jp/publications.html

    • Related Report
      2013 Annual Research Report
  • [Remarks]

    • URL

      http://bioimaging.ifrec.osaka-u.ac.jp/

    • Related Report
      2011 Annual Research Report
  • [Remarks]

    • URL

      http://bioimaging.ifrec.osaka-u.ac.jp

    • Related Report
      2010 Annual Research Report
  • [Patent(Industrial Property Rights)] 新規抗腫瘍剤及びそのスクリーニング方法2012

    • Inventor(s)
      石井優, 他
    • Industrial Property Rights Holder
      国立大学法人大阪大学
    • Industrial Property Number
      2012-015982
    • Filing Date
      2012-01-30
    • Related Report
      2011 Annual Research Report
  • [Patent(Industrial Property Rights)] 新規骨吸収抑制剤のスクリーニング方法2010

    • Inventor(s)
      石井優
    • Industrial Property Rights Holder
      国立大学法人大阪大学
    • Filing Date
      2010-11-10
    • Related Report
      2010 Annual Research Report
    • Overseas

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Published: 2010-08-23   Modified: 2019-07-29  

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