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Development of fluorescent probes for visualizing low-pH environment and their application in intravital imaging

Research Project

Project/Area Number 24750160
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Chemistry related to living body
Research InstitutionOsaka University

Principal Investigator

KOWADA Toshiyuki  大阪大学, 免疫学フロンティア研究センター, 特任助教 (40584397)

Project Period (FY) 2012-04-01 – 2014-03-31
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2013: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Fiscal Year 2012: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Keywords破骨細胞 / 蛍光プローブ / イメージング / pH感受性 / BODIPY / 生体イメージング
Research Abstract

To perform intravital fluorescence imaging of osteoclasts, which relate to bone diseases such as rheumatoid arthritis and osteoporosis, we developed fluorescent probes that can visualize low-pH region created during bone resorption. A bisphosphonate group and photo-induced electron transfer mechanism were used for the delivery and controlling pH-dependent fluorescence of the probes. In addition, we achieved long-term imaging of osteoclast activity in vivo with improved probe that has electron-withdrawing groups to enhance its photostability. Furthermore, we succeeded to develop the fluorescent probes with red-shifted emission maxima.

Report

(3 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Research-status Report
  • Research Products

    (36 results)

All 2014 2013 2012 Other

All Journal Article (1 results) (of which Peer Reviewed: 1 results) Presentation (30 results) Book (2 results) Remarks (3 results)

  • [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 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Presentation] 長波長蛍光を有するpH感受性蛍光プローブの開発2014

    • Author(s)
      前田拓樹,小和田俊行,菊地和也
    • Organizer
      日本化学会第94春季年会
    • Place of Presentation
      名古屋大学東山キャンパス(名古屋, 愛知)
    • Year and Date
      2014-03-28
    • Related Report
      2013 Final Research Report
  • [Presentation] Real-time Visualization of Osteoclast Activity in Living Mice with pH-Activatable Fluorescent Probe2014

    • Author(s)
      Hiroki Maeda, Toshiyuki Kowada, Kazuya Kikuchi
    • Organizer
      Imaging and Sensing Biomolecular Function and Assembly
    • Place of Presentation
      Institut Européen de Chimie et Biologie, University of Bordeaux (Pessac, France)
    • Year and Date
      2014-03-14
    • Related Report
      2013 Final Research Report
  • [Presentation] Real-time Visualization of Osteoclast Activity in Living Mice with pH-Activatable Fluorescent Probe2014

    • Author(s)
      Hiroki Maeda, Toshiyuki Kowada, Kazuya Kikuchi
    • Organizer
      Imaging and Sensing Biomolecular Function and Assembly
    • Place of Presentation
      Institut Europeen de Chimie et Biologie, University of Bordeaux, Pessac, France
    • Related Report
      2013 Annual Research Report
  • [Presentation] 長波長蛍光を有するpH感受性蛍光プローブの開発2014

    • Author(s)
      前田拓樹、小和田俊行、菊地和也
    • Organizer
      日本化学会第94春季年会
    • Place of Presentation
      名古屋大学 東山キャンパス、名古屋、愛知
    • Related Report
      2013 Annual Research Report
  • [Presentation] Development of pH-Activatable Fluorescent Probe and Intravital Imaging of Osteoclast2013

    • Author(s)
      Toshiyuki Kowada, Hiroki Maeda, Kazuya Kikuchi
    • Organizer
      First Osaka University-EPFL International Symposium
    • Place of Presentation
      Icho Kaikan (Osaka University, Suita, Osaka, Japan)
    • Year and Date
      2013-12-02
    • Related Report
      2013 Final Research Report
  • [Presentation] Development of Highly Photostable Fluorescent Probe for Visualizing Osteoclast Activity in Vivo2013

    • Author(s)
      Hiroki Maeda, Toshiyuki Kowada, Kazuya Kikuchi
    • Organizer
      International Symposium Towards Comprehensive Understanding of Immune Dynamism (TCUID 2013)
    • Place of Presentation
      Osaka University (Suita, Osaka, Japan)
    • Year and Date
      2013-11-19
    • Related Report
      2013 Final Research Report
  • [Presentation] Real-time Visualization of Osteoclast Activity in Living Mice2013

    • Author(s)
      Hiroki Maeda, Toshiyuki Kowada, Kazuya Kikuchi
    • Organizer
      ICBS2013 (the 2nd official conference of the International Chemical Biology Society)
    • Place of Presentation
      Shirankaikan (Kyoto, Japan)
    • Year and Date
      2013-10-08
    • Related Report
      2013 Final Research Report
  • [Presentation] pH感受性蛍光プローブの開発と破骨細胞イメージングへの応用2013

    • Author(s)
      小和田俊行,前田拓樹,菊地和也
    • Organizer
      第22回日本バイオイメージング学会学術集会
    • Place of Presentation
      東京大学薬学部講堂(東京)
    • Year and Date
      2013-09-15
    • Related Report
      2013 Final Research Report
  • [Presentation] pH感受性蛍光プローブを用いた破骨細胞活性の生体イメージング2013

    • Author(s)
      小和田俊行,前田拓樹,菊地和也
    • Organizer
      日本ケミカルバイオロジー学会第8回年会
    • Place of Presentation
      東京医科歯科大学(東京)
    • Year and Date
      2013-06-21
    • Related Report
      2013 Final Research Report
  • [Presentation] Development of Chemical Probes for Fluorescence Imaging of Bone-Resorbing Osteoclast in Living Mice2013

    • Author(s)
      Toshiyuki Kowada, Kazuya Kikuchi
    • Organizer
      Gordon Research Conference on Bioorganic Chemistry
    • Place of Presentation
      Proctor Academy (Andover, New Hampshire, USA)
    • Year and Date
      2013-06-12
    • Related Report
      2013 Final Research Report
  • [Presentation] Design of pH-Activatable Fluorescent Probes with High Photostability2013

    • Author(s)
      Hiroki Maeda, Toshiyuki Kowada, Kazuya Kikuchi
    • Organizer
      Gordon Research Conference on Bioorganic Chemistry
    • Place of Presentation
      Proctor Academy (Andover, New Hampshire, USA)
    • Year and Date
      2013-06-10
    • Related Report
      2013 Final Research Report
  • [Presentation] 生体内の破骨細胞活性を可視化するpH感受性蛍光プローブの開発2013

    • Author(s)
      前田拓樹,小和田俊行,菊地和也
    • Organizer
      日本分子イメージング学会第8回学術集会
    • Place of Presentation
      横浜赤レンガ倉庫1号館(横浜, 神奈川)
    • Year and Date
      2013-05-31
    • Related Report
      2013 Final Research Report
  • [Presentation] 破骨細胞の動態イメージングを目指したpH感受性蛍光プローブの開発2013

    • Author(s)
      前田拓樹,小和田俊行,菊地和也
    • Organizer
      日本化学会第93春季年会
    • Place of Presentation
      立命館大学びわこくさつキャンパス(草津, 滋賀)
    • Year and Date
      2013-03-23
    • Related Report
      2013 Final Research Report
  • [Presentation] 生体内の破骨細胞活性を可視化するpH感受性蛍光プローブの開発2013

    • Author(s)
      前田拓樹、小和田俊行、菊地和也
    • Organizer
      日本分子イメージング学会第8回学術集会
    • Place of Presentation
      横浜赤レンガ倉庫1号館、横浜、神奈川
    • Related Report
      2013 Annual Research Report
  • [Presentation] Development of Chemical Probes for Fluorescence Imaging of Bone-Resorbing Osteoclast in Living Mice2013

    • Author(s)
      Toshiyuki Kowada, Kazuya Kikuchi
    • Organizer
      Gordon Research Conference on Bioorganic Chemistry
    • Place of Presentation
      Proctor Academy, Andover, New Hampshire, USA
    • Related Report
      2013 Annual Research Report
  • [Presentation] Design of pH-Activatable Fluorescent Probes with High Photostability2013

    • Author(s)
      Hiroki Maeda, Toshiyuki Kowada, Kazuya Kikuchi
    • Organizer
      Gordon Research Conference on Bioorganic Chemistry
    • Place of Presentation
      Proctor Academy, Andover, New Hampshire, USA
    • Related Report
      2013 Annual Research Report
  • [Presentation] pH感受性蛍光プローブを用いた破骨細胞活性の生体イメージング2013

    • Author(s)
      小和田俊行、前田拓樹、菊地和也
    • Organizer
      日本ケミカルバイオロジー学会 第8回年会
    • Place of Presentation
      東京医科歯科大学、東京
    • Related Report
      2013 Annual Research Report
  • [Presentation] pH感受性蛍光プローブの開発と破骨細胞イメージングへの応用2013

    • Author(s)
      小和田俊行、前田拓樹、菊地和也
    • Organizer
      第22回 日本バイオイメージング学会学術集会
    • Place of Presentation
      東京大学薬学部講堂、東京
    • Related Report
      2013 Annual Research Report
  • [Presentation] Real-time Visualization of Osteoclast Activity in Living Mice2013

    • Author(s)
      Hiroki Maeda, Toshiyuki Kowada, Kazuya Kikuchi
    • Organizer
      ICBS2013 (the 2nd official conference of the International Chemical Biology Society)
    • Place of Presentation
      Shirankaikan, Kyoto, Japan
    • Related Report
      2013 Annual Research Report
  • [Presentation] Development of Highly Photostable Fluorescent Probe for Visualizing Osteoclast Activity in Vivo2013

    • Author(s)
      Hiroki Maeda, Toshiyuki Kowada, Kazuya Kikuchi
    • Organizer
      International Symposium Towards Comprehensive Understanding of Immune Dynamism (TCUID 2013)
    • Place of Presentation
      Osaka University, Suita, Osaka, Japan
    • Related Report
      2013 Annual Research Report
  • [Presentation] Development of pH-Activatable Fluorescent Probe and Intravital Imaging of Osteoclast2013

    • Author(s)
      Toshiyuki Kowada, Hiroki Maeda, Kazuya Kikuchi
    • Organizer
      First Osaka University-EPFL International Symposium
    • Place of Presentation
      Osaka University, Suita, Osaka, Japan
    • Related Report
      2013 Annual Research Report
  • [Presentation] 破骨細胞の動態イメージングを目指したpH感受性蛍光プローブの開発2013

    • Author(s)
      前田拓樹、小和田俊行、菊地和也
    • Organizer
      日本化学会第93春季年会
    • Place of Presentation
      立命館大学 びわこくさつキャンパス, 草津市, 滋賀
    • Related Report
      2012 Research-status Report
  • [Presentation] Development of Chemical Probes for in Vivo Fluorescence Imaging of Bone-Resorbing Osteoclast2012

    • Author(s)
      Toshiyuki Kowada, Hiroki Maeda, Kazuya Kikuchi
    • Organizer
      International Symposium Towards Comprehensive Understanding of Immune Dynamism (TCUID 2012)
    • Place of Presentation
      Icho Kaikan (Osaka University, Suita, Osaka, Japan)
    • Year and Date
      2012-10-30
    • Related Report
      2013 Final Research Report
  • [Presentation] Development of pH-activatable Fluorescence Probe for Bone-Resorbing Osteoclasts in Living Mice2012

    • Author(s)
      Hiroki Maeda, Toshiyuki Kowada, Kazuya Kikuchi
    • Organizer
      World Molecular Imaging Congress 2012
    • Place of Presentation
      Convention Centre Dublin (Dublin, Ireland)
    • Year and Date
      2012-09-08
    • Related Report
      2013 Final Research Report
  • [Presentation] マウス体内における破骨細胞の骨吸収を可視化するpH感受性蛍光プローブの開発2012

    • Author(s)
      小和田俊行,前田拓樹,菊地和也
    • Organizer
      第6回バイオ関連化学シンポジウム
    • Place of Presentation
      北海道大学高等教育推進機構(札幌, 北海道)
    • Year and Date
      2012-09-06
    • Related Report
      2013 Final Research Report
  • [Presentation] In vivoで破骨細胞活性を可視化するpH感受性蛍光プローブの開発2012

    • Author(s)
      前田拓樹,小和田俊行,菊地和也
    • Organizer
      日本ケミカルバイオロジー学会第7回年会
    • Place of Presentation
      京都大学百周年時計台記念館(京都, 京都)
    • Year and Date
      2012-06-07
    • Related Report
      2013 Final Research Report
  • [Presentation] In vivoで破骨細胞活性を可視化するpH感受性蛍光プローブの開発2012

    • Author(s)
      前田拓樹、小和田俊行、菊地和也
    • Organizer
      日本ケミカルバイオロジー学会 第7回年会
    • Place of Presentation
      京都大学 百周年時計台記念館, 京都市, 京都
    • Related Report
      2012 Research-status Report
  • [Presentation] マウス体内における破骨細胞の骨吸収を可視化するpH感受性蛍光プローブの開発2012

    • Author(s)
      小和田俊行、前田拓樹、菊地和也
    • Organizer
      第6回バイオ関連化学シンポジウム
    • Place of Presentation
      北海道大学 高等教育推進機構, 札幌市, 北海道
    • Related Report
      2012 Research-status Report
  • [Presentation] Development of pH-activatable Fluorescence Probe for Bone-Resorbing Osteoclasts in Living Mice2012

    • Author(s)
      Hiroki Maeda, Toshiyuki Kowada, Kazuya Kikuchi
    • Organizer
      World Molecular Imaging Congress 2012
    • Place of Presentation
      Convention Centre Dublin, Dublin, Ireland
    • Related Report
      2012 Research-status Report
  • [Presentation] Development of Chemical Probes for in Vivo Fluorescence Imaging of Bone-Resorbing Osteoclast2012

    • Author(s)
      Toshiyuki Kowada, Hiroki Maeda, Kazuya Kikuchi
    • Organizer
      International Symposium Towards Comprehensive Understanding of Immune Dynamism (TCUID 2012)
    • Place of Presentation
      Icho Kaikan, Osaka University, Suita, Osaka
    • Related Report
      2012 Research-status Report
  • [Book] 「5. in vivoイメージングに適した化学プローブの選択」, 実験医学別冊「in vivoイメージング実験プロトコール原理と導入のポイントから2光子顕微鏡の応用まで」(石井優/編)2012

    • Author(s)
      小和田俊行, 菊地和也
    • Publisher
      羊土社
    • Related Report
      2013 Final Research Report
  • [Book] 実験医学別冊「in vivoイメージング実験プロトコール 原理と導入のポイントから2光子顕微鏡の応用まで」 5章 in vivoイメージングに適した化学プローブの選択2012

    • Author(s)
      小和田俊行、菊地和也
    • Publisher
      羊土社
    • Related Report
      2012 Research-status Report
  • [Remarks]

    • URL

      http://www-molpro.mls.eng.osaka-u.ac.jp/

    • Related Report
      2013 Final Research Report
  • [Remarks] 大阪大学大学院工学研究科 生命先端工学専攻物質生命工学コース 菊地研究室

    • URL

      http://www-molpro.mls.eng.osaka-u.ac.jp/

    • Related Report
      2013 Annual Research Report
  • [Remarks] 大阪大学大学院工学研究科 菊地研究室

    • URL

      http://www-molpro.mls.eng.osaka-u.ac.jp/

    • Related Report
      2012 Research-status Report

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Published: 2013-05-31   Modified: 2019-07-29  

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