Dynamic in vivo imaging of osteoclast functions for development of novel therapeutics against bone-resorptive disorders

• Project/Area Number: 20790708
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: 膠原病・アレルギー・感染症内科学
• Research Institution: National Hospital Organization Osaka-Minami Medical Center
• Principal Investigator: ISHII Masaru National Hospital Organization Osaka-Minami Medical Center, 免疫学フロンティア研究センター, 特任准教授 (10324758)
• Project Period (FY): 2008 – 2009
• Project Status: Completed (Fiscal Year 2009)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2009: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2008: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 細胞・組織 / シグナル伝達 / 医療・福祉 / 薬理学 / トランスレーショナルリサーチ / 破骨細胞 / イメージング / 関節リウマチ / ケモカイン / 脂質メディエーター / 骨粗鬆症 / 細胞動態 / 骨代謝

Research Abstract

Osteoclasts are the only somatic cells with bone-resorbing capacity, and they play a critical role not only in normal bone homeostasis but also in the pathogenesis of bone destructive disorders such as rheumatoid arthritis and osteoporosis. To reveal the process of recruitment of osteoclast precursors to bone surface, I have exploited a new experimental method using intravital two-photon microscopy for bone tissues that have been originally developed. One of the specific subjects was the migration and positioning of osteoclast precursors by a combination of lipid mediator such as SIP and bone marrow chemokines. I believe this study provided a new concept in a variety of research field, and, beyond it basic implication, the findings led to insights into human diseases and the therapeutics.

Research Products

• [Journal Article] Sphingosine-1-phosphate mobilizes osteoclast precursors and regulates bone homeostasis (2009)
  • Author(s): Ishii M, Egen JG, Klauschen F, Meier-Schellersheim M, Saeki Y, Vacher J, Praia RL, Germain RN
  • Journal Title: Nature 458(7237) Pages: 524-528
• [Journal Article] Quantifying cellular interaction dynamics in 3-D fluorescence microscopy data (2009)
  • Author(s): Klauschen F, Ishii M, Qi H, Bajenoff M, Egen JG, Germain RN, Meier-Schellersheim M
  • Journal Title: Nature Protoc. 4(9) Pages: 1305-1311
• [Journal Article] Visualization and identification of IL-7 producing cells in reporter mice (2009)
  • Author(s): Mazzucchelli R. Warming S, Lawrence SM, Ishii M, Abshari M, Feigenbaum L, Washington AV, Warner AC, Sims DJ, Li WQ, Hixon JA, Gray DUD, Rich BE, Morrow M, Anver MR, Cherry J, Naf D, Sternberg LR, McVicar DW, Farr AG, Germain RN, Rogers K, Copeland N, Durum SK
  • Journal Title: PLoS One 4(11)
• [Journal Article] Sphingosine-1-phosphate mobilizes osteoclast precursors and regulates bone homeostasis. (2009)
  • Author(s): Ishii, et al.
  • Journal Title: Nature 458 Pages: 524-528
  • Peer Reviewed
• [Journal Article] Quantifying cellular interaction dynamics in 3-D fluorescence microscopy data. (2009)
  • Author(s): Klauschen, Ishii, et al.
  • Journal Title: Nature Protocols 4 Pages: 1305-1311
  • Peer Reviewed
• [Journal Article] Visualization and identification of IL-7 producing cells in reporter mice. (2009)
  • Author(s): Mazzucchelli, Ishii, et al.
  • Journal Title: PLoS One 4
  • Peer Reviewed
• [Journal Article] Sphingosine-1-phosphate mobilizes osteoclast precursors and regulates bone homeostasis (2009)
  • Author(s): Ishii M, et al.
  • Journal Title: Nature (published online)
  • Peer Reviewed
• [Journal Article] Osteoclastc ell fusion: Mechanisms and molecules (2008)
  • Author(s): Ishii M, Saeki Y.
  • Journal Title: Mod Rheumatol. 18 Pages: 220-227
  • NAID: 10024150622
  • Peer Reviewed
• [Journal Article] Abundante xpression of tetraspanin CD9 in activated osteoclasts in ovariectomy-induced osteoporosis… (2008)
  • Author(s): Iwai K, et al.
  • Journal Title: Rheumatol Int. 8 Pages: 225-231
  • Peer Reviewed
• [Presentation] Dynamics of osteoclast precursor migration visualized by in vivo bone imaging: A novel point of control for bone homeostasis (2010)
  • Author(s): Masaru Ishii
  • Organizer: The 14th International Conferences on Endocrinology 2010(ICE2010)
  • Place of Presentation: 大阪
  • Year and Date: 2010-03-31
• [Presentation] Chemokine-mediated migration control of osteoclast precursors visualized by intravital bone imaging: A novel point of regulation for bone homeostasis (2010)
  • Author(s): Masaru Ishii
  • Organizer: The 14th International Conferences on Endocrinology 2010(ICE2010)
  • Place of Presentation: 京都
  • Year and Date: 2010-03-26
• [Presentation] Chemokine-mediated migration control of osteoclast precursors visualized by dynamic in vivo bone imaging: A novel point of regulation for bone homeostasis (2010)
  • Author(s): 石井優
  • Organizer: 第83日本薬理学会年会
  • Place of Presentation: 大阪
  • Year and Date: 2010-03-16
• [Presentation] Chemokine and lipid mediator-mediated control of osteoclast migration visualized by in vivo bone imaging : A novel point of regulation for bone homeostasis. (2010)
  • Author(s): Masaru Ishii
  • Organizer: International Bone and Mineral Society
  • Place of Presentation: Davos (Switzerland)
  • Year and Date: 2010-03-16
• [Presentation] Chemokine and lipid mediator-mediated control of osteoclast migration visualized by in vivo bone imaging: A novel point of regulation for bone homeostasis (2010)
  • Author(s): Masaru Ishii
  • Organizer: International Bone and Mineral Society (IBMS)
  • Year and Date: 2010-03-14
• [Presentation] 二光子励起顕微鏡を駆使した骨組織内のインビボ光イメージング～破骨細胞分化・骨吸収の新しい調節作用点の発見～ (2009)
  • Author(s): 石井優
  • Organizer: 第31日本分子生物学会大会
  • Place of Presentation: 横浜
  • Year and Date: 2009-12-12
• [Presentation] Dynamic in vivo visualizahon of osteoclast precursor migration in living bones elucidating a novel regulatory point for 'osteoimmunologY' (2009)
  • Author(s): 石井優
  • Organizer: 第39日本免疫学会大会
  • Year and Date: 2009-12-03
• [Presentation] スフィンゴシン1リン酸による破骨前駆細胞の遊走・位置決めの制御機構～生体多光子励起顕微鏡を用いた骨組織内のin vivoイメージングより～ (2009)
  • Author(s): 石井優
  • Organizer: 第82回・日本生化学会大会
  • Place of Presentation: 神戸
  • Year and Date: 2009-10-23
• [Presentation] 骨組織のライブイメージング～その方法論と今後の応用～ (2009)
  • Author(s): 石井優
  • Organizer: 第27回・日本骨代謝学会
  • Place of Presentation: 大阪
  • Year and Date: 2009-07-24
• [Presentation] ～見てみて分かった破骨細胞の遊走と位置決めの制御機構～骨組織の生体二光子励起顕微鏡イメージングより (2009)
  • Author(s): 石井優
  • Organizer: 免疫サマースクール2009
  • Place of Presentation: 淡路
  • Year and Date: 2009-07-16
• [Presentation] Dynamics of osteoclast precursor migration visualized by in viva bone imaging: A novel point of control for osteoimmunoIogy (2009)
  • Author(s): Masaru Ishii
  • Organizer: 第3回・GCOE国際シンポジウム
  • Place of Presentation: 東京医科歯科大学
  • Year and Date: 2009-06-11
• [Presentation] SIP-mediated migration control of osteoclast precursors visualized by in vivo bone imaging: A novel point of regulation for bone metabolism (2009)
  • Author(s): Masaru Ishii
  • Organizer: PLM2009(国際学会)
  • Place of Presentation: 東京
  • Year and Date: 2009-05-27
• [Presentation] Chemokine-mediated migration control of osteoclast precursors visualized by in vivo bone imaging: A novel point of regulation for osteoimmunology (2009)
  • Author(s): Masaru Ishii
  • Organizer: 第2回・IFReC国際シンポジウム
  • Place of Presentation: 大阪
  • Year and Date: 2009-02-11
• [Presentation] 脂質メディエーターやケモカインによる破骨細胞前駆細胞の遊走・位置決めの制御〜生体多光子励起顕微鏡を用いた骨組織のin vivoイメージングより〜 (2008)
  • Author(s): 石井優
  • Organizer: 日本生化学・分子生物学合同大会・シンポジウム
  • Place of Presentation: 神戸国際会議場
  • Year and Date: 2008-12-11
• [Presentation] 脂質メディエーターやケモカインによる破骨細胞前駆細胞の遊走・位置決めの制御～生体多光子励起顕微鏡を用いた骨組織のin vivOイメージングより～ (2008)
  • Author(s): 石井優
  • Organizer: BMB2008(生化学・分子生物学会合同大会)
  • Place of Presentation: 神戸
  • Year and Date: 2008-12-10
• [Presentation] Chemokine-mediated migration control of osteoclast precursors visualized by in vivo bone imaging: A novel point of control for bone homeostasis (2008)
  • Author(s): Masaru Ishii
  • Organizer: 6th Bone Biology Forum
  • Place of Presentation: 静岡県裾野市
  • Year and Date: 2008-08-21
• [Remarks]
  • URL: http://bioimaging.ifrec.osaka-u.ac.jp/
• [Remarks]
  • URL: http://www.ifrec.osaka-u.ac.jp/jpn/laboratory/biologicaliimaging/index.php
• [Remarks]
  • URL: http://bioimaging.ifrec.osaka-u.ac.jp
• [Patent(Industrial Property Rights)] 新規骨吸収抑制剤のスクリーニング方法 (2009)
  • Inventor(s): 石井優
  • Industrial Property Rights Holder: 国立大学法人大阪大学
  • Industrial Property Number: 2009-260655
  • Filing Date: 2009-11-16
• [Patent(Industrial Property Rights)] 脂質メディエーターやケモカインを標的とした骨吸収性疾患に対する新規治療法 (2009)
  • Inventor(s): 石井優
  • Industrial Property Rights Holder: 大阪大学
  • Industrial Property Number: 2009-260655
  • Filing Date: 2009-11-16