Systematic analyses of modes of migration, differentiation andfunction of bone-resorbing osteoclasts visualized by intravitalimaging

• Project/Area Number: 22689030
• Research Category: Grant-in-Aid for Young Scientists (A)
• Allocation Type: Single-year Grants
• Research Field: 膠原病・アレルギー・感染症内科学
• Research Institution: Osaka University
• Principal Investigator: ISHII Masaru 大阪大学, 免疫学フロンティア研究センター, 特任教授 (10324758)
• Project Period (FY): 2010 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥19,630,000 (Direct Cost: ¥15,100,000、Indirect Cost: ¥4,530,000); Fiscal Year 2012: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000); Fiscal Year 2011: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000); Fiscal Year 2010: ¥6,630,000 (Direct Cost: ¥5,100,000、Indirect Cost: ¥1,530,000)
• Keywords: リウマチ学 / 骨代謝 / 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

Research Abstract

The main subject of this study is to reveal the cellular dynamics in various kinds of tissues and organs in vivo, by using advanced imaging techniques, especially focusing on the dynamic phenomenon within bone marrow cavity. By improving the optical technology, we developed an intravital bone imaging system that enabled elucidation of control mechanisms for dynamic behaviors of bone-resorbing osteoclasts in vivo. We also developed novel anti-bone resorptive treatments based on our findings.

Research Products

• [Journal Article] Depletion of Jarid1b induces cellular senescence in human colorectal cancer (2013)
  • Author(s): Ohta K, Haraguchi N, Kano Y, Kagawa Y, Konno M, Nishikawa S, Hamabe A, Hasegawa S, Ogawa H, Fukusumi T, Uemura M, Nishimura J, Hata T, Takemasa I, Mizushima T, Noguchi Y, Ozaki M, Kudo T, Sakai D, Satoh T, Fukami M, Ishii M, Yamamoto H, Doki Y, Mori M, Is
  • Journal Title: Int. J. Oncol Volume: 42(4) Pages: 1212-8
  • Peer Reviewed
• [Journal Article] Systemic circulation and bone recruitment of osteoclast precursors tracked by using fluorescent imaging techniques (2013)
  • Author(s): Kotani M, Kikuta J, Klauschen F, Chino T, Kobayashi Y, Yasuda H, Tamai K, Miyawaki A, Kanagawa O, Tomura M, Ishii M
  • Journal Title: J. Immunol Volume: 190(2) Pages: 605-12
  • Peer Reviewed
• [Journal Article] Dynamic visualization of RANKL and Th17-mediated osteoclast function (2013)
  • Author(s): Kikuta J, Wada Y, Kowada T, Wang Z, Sun-Wada G-H, Nishiyama I, Mizukami S, Maiya N, Yasuda H, Kumanogoh A, Kikuchi K, Germain RN, Ishii M
  • Journal Title: J. Clin. Invest Volume: 123(2) Pages: 866-873
  • Peer Reviewed
• [Journal Article] Layer V cortical neurons require microglial support for survival during postnatal development (2013)
  • Author(s): Ueno M, Fujita Y, Tanaka T, Nakamura Y, Kikuta J, Ishii M, Yamashita T
  • Journal Title: Nat. Neurosci Volume: 16(5) Pages: 543-51
  • Peer Reviewed
• [Journal Article] CognitionMaster: An Object-Based Image Analysis Framework (2013)
  • Author(s): Wienert S, Heim D, Kotani M, Lindequist B, Stenzinger A, Ishii M, Hufnagl P, Beil M, Dietel M, Denkert C, Klauschen F
  • Journal Title: Diagn. Pathol Volume: 8 Pages: 34-34
  • Peer Reviewed
• [Journal Article] Dynamic analysis of histamine-mediated attenuation of acetylcholine-induced sweating via GSK3beta activation (2013)
  • Author(s): Matsui S, Murota H, Takahashi A, Yang A, Lee J-B, Omiya K, Ohmi M, Kikuta J, Ishii M, Katayama I
  • Journal Title: J. Invest. Dermatol
  • Peer Reviewed
• [Journal Article] Sphingosine-1-phosphate signaling controlling osteoclasts and bone homeostasis (2013)
  • Author(s): Ishii M, Kikuta J
  • Journal Title: Biochim Biophys Acta Volume: 1831(1) Pages: 223-227
  • 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(17) Pages: 7009-13
  • Peer Reviewed
• [Journal Article] Osteoclast migration, differentiation, and function: novel therapeutic targets for rheumatic diseases (2013)
  • Author(s): Kikuta J, Ishii M
  • Journal Title: Rheumatology Volume: 52(2) Pages: 226-34
  • Peer Reviewed
• [Journal Article] Dynamic live imaging of bone: opening a new era with 'bone histodynametry' (2013)
  • Author(s): Ishii M, Fujimori S, Kaneko T, Kikuta J.
  • Journal Title: J Bone Miner Metab
  • Peer Reviewed
• [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
  • 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
  • Peer Reviewed
• [Journal Article] Recent advances in intravital imaging of dynamic biological systems (2012)
  • Author(s): Kikuta J, Ishii M.
  • Journal Title: J. Pharmacol. Sci Volume: 119(3) Pages: 193-7
  • NAID: 10030986703
  • Peer Reviewed
• [Journal Article] How do contemporaryimaging techniques contribute to basic and clinical rheumatology? (2012)
  • Author(s): Ishii M
  • Journal Title: Ann. Rheum. Dis Volume: 71 (Suppl 2)
  • Peer Reviewed
• [Journal Article] Use of intravital microscopy and in vitro chemotaxis assays to study the roles of sphingosine-1-phosphate in bone homeostasis (2012)
  • Author(s): Ishii T, Kawamura S, Nishiyama I, Kikuta J, Ishii M
  • Journal Title: Methods Mol. Biol. Volume: 874 Pages: 129-139
  • Peer Reviewed
• [Journal Article] The sphingosine-1-phosphate transporter Spns2 expressed on endothelial cells regulates lymphocyte trafficking in mice (2012)
  • Author(s): Fukuhara S, Simmons S, Kawamura S, Inoue A, Orba Y, Tokudome T, Sunden Y, Arai Y, Moriwaki K, Ishida J, Uemura A, Kiyonari H, Abe T, Fukamizu A, Hirashima M, Sawa H, Aoki J, Ishii M*, Mochizuki N*
  • Journal Title: J. Clin. Invest Volume: 122(4) Pages: 1416-1426
  • Peer Reviewed
• [Journal Article] Intestinal CX3C chemokine receptor 1high (CX3CR1high) myeloid cells prevent T-cell-dependent colitis (2012)
  • Author(s): Kayama H, Ueda Y, Sawa Y, Jeon SG, Ma JS, Okumura R, Kubo A, Ishii M, Okazaki T, Murakami M, Yamamoto M, Yagita H, Takeda K
  • Journal Title: Proc. Natl. Acad. Sci. USA Volume: 109(13) Pages: 5010-5015
  • 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
  • Peer Reviewed
• [Journal Article] The sphingosine-1-phosphate transporter Spns2 expressed on endothelial cells regulates lymphocyte trafficking in mice (2012)
  • 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
  • Peer Reviewed
• [Journal Article] In vivo fluorescence imaging of bone-resorbing osteoclasts (2011)
  • Author(s): Kowada T, Kikuta, J, Kubo A, Ishii M, Maeda H, Mizukami S, Kikuchi K
  • Journal Title: J. Am. Chem. Soc Volume: 33(44) Pages: 17772-17776
  • 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 T, Shimazu Y, Nishiyama I, Kikuta J, Ishii M
  • Journal Title: Mol. Cells Volume: 31(5) Pages: 399-403
  • Peer Reviewed
• [Journal Article] PDGFRα-positive cells in bone marrow are mobilized by HMGB1 to regenerate injured epithelia (2011)
  • Author(s): Tamai K, Yamazaki T, Chino T, Ishii M, Otsuru S, Kikuchi Y, Iinuma S, Saga K, Nimura K, Shimbo T, Umegaki N, Katayama I, Miyazaki J, Takeda J, McGrath J, Uitto J, Kaneda Y.
  • Journal Title: Proc. Natl. Acad. Sci. USA Volume: 108(16) Pages: 6609-6614
  • Peer Reviewed
• [Journal Article] S1P-targeted therapy for elderly rheumatoid arthritis patients with osteoporosis (2011)
  • Author(s): Kikuta J, Iwai K, Saeki Y, Ishii M
  • Journal Title: Rheumatol. Int Volume: 31 Pages: 967-969
  • Peer Reviewed
• [Journal Article] In Vivo Fluorescence Imaging of Bone-Resorbing Osteoclasts (2011)
  • 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
  • Peer Reviewed
• [Journal Article] S1P-targeted therapy for elderly rheumatoid arthritis patients with osteoporosis (2011)
  • Author(s): Kikuta, et al
  • Journal Title: Rheumatol.Int. Volume: 31 Issue: 7 Pages: 967-969
  • DOI: 10.1007/s00296-010-1634-8
  • 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)
  • 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)
  • Peer Reviewed
• [Journal Article] Chemorepulsion by blood S1P regulates osteoclast precursor mobilization and bone remodeling in vivo (2010)
  • Author(s): Ishii M, Kikuta J, Shimazu Y, Meier-Schellersheim M, Germain RN
  • Journal Title: J. Exp. Med Volume: 207 Pages: 2793-2798
  • Peer Reviewed
• [Journal Article] Control of osteoclast precursor migration: A novel point of control for osteoclastogenesis and bone homeostasis (2010)
  • Author(s): Ishii T, Kikuta J, Kubo A, Ishii M
  • Journal Title: IBMS BoneKey Volume: 7 Pages: 279-286
  • Peer Reviewed
• [Journal Article] Intravital two-photon imaging: A versatile tool for dissecting the immune system (2010)
  • Author(s): Ishii T, Ishii M.
  • Journal Title: Ann. Rheum. Dis Volume: 70 (Suppl 1)
  • 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
  • Peer Reviewed
• [Presentation] Roles of S1P in osteoclast regulation and bone physiology (2012)
  • Author(s): Ishii M
  • Organizer: 2012 Gordon Research Conference
  • Place of Presentation: Il Ciocco, Italy
  • Year and Date: 2012-04-24
• [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
  • Invited
• [Presentation] Dynamic behaviors of osteoclast function visualized by intravital imaging (2012)
  • Author(s): Masaru Ishii
  • Organizer: Cold Spring Harbor Asia Conference
  • Place of Presentation: Suzhou, China
  • Invited
• [Presentation] Roles of S1P in osteoclast regulation and bone remodeling (2011)
  • Author(s): Ishii M
  • Organizer: 2011 FASEB Summer Research Conference
  • Place of Presentation: Il Ciocco, Italy
  • Year and Date: 2011-08-18
• [Presentation] Roles of S1P in osteoclast regulation and bone remodeling (2011)
  • Author(s): Masaru Ishii
  • Organizer: 2011 FASEB Summer Research Conference
  • Place of Presentation: II Ciocco, Italy(招待講演)
  • Year and Date: 2011-08-18
• [Presentation] Chemokine-mediated migration control of osteoclast precursors visualized by live bone imaging (2010)
  • Author(s): Ishii M
  • Organizer: 3rd International Conference of Osteoimmunology
  • Place of Presentation: Santorini, Greece
  • Year and Date: 2010-06-21
• [Presentation] Chemokine-mediated migration control of osteoclast precursors visualized by live bone imaging (2010)
  • 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
• [Remarks]
  • URL: http://www.icb.med.osaka-u.ac.jp/http://bioimaging.ifrec.osaka-u.ac.jp/
• [Remarks]
  • URL: http://bioimaging.ifrec.osaka-u.ac.jp/
• [Remarks]
  • URL: http://bioimaging.ifrec.osaka-u.ac.jp
• [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,賀川義規,森 正樹,石井秀始
  • Industrial Property Rights Holder: 国立大学法人大阪大学
  • Industrial Property Number: 2012-015982
  • Filing Date: 2012-01-30
• [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
• [Patent(Industrial Property Rights)] 画像処理装置および方法、並びにプログラム (2011)
  • Inventor(s): 石井 優,菊田順一,米谷信男
  • Industrial Property Rights Holder: 国立大学法人大阪大学・ニコン株式会社
  • Industrial Property Number: 2011-232479
  • Filing Date: 2011-10-24
• [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
  • Overseas
• [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