The pathophysiology of rheumatoid arthritis elucidated by intravital multiphoton imaging

• Project/Area Number: 25893117
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Single-year Grants
• Research Field: Collagenous pathology/Allergology
• Research Institution: Osaka University
• Principal Investigator: KIKUTA Junichi 大阪大学, 医学(系)研究科(研究院), 助教 (60710069)
• Project Period (FY): 2013-08-30 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 関節リウマチ / 生体イメージング / 破骨細胞

Outline of Final Research Achievements

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by synovial joint inflammation and progressive cartilage/bone destruction. Arthritic bone destruction is considered to be mediated mainly by enhanced activation of osteoclasts at inflammatory sites. In this study, I established the advanced imaging system to visualize the cellular dynamics in arthritic joints with intravital multiphoton microscopy. By means of this system, I succeeded in visualization of abnormally activated osteoclasts in arthritic inflammation and bone destruction. Furthermore I revealed the in vivo effects of biologic agents on osteoclast function. This imaging approach would be beneficial for studying the pathophysiology of RA in vivo and would thus be useful for evaluating novel anti-rheumatic drugs.

Research Products

• [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
  • 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
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Intravital multiphoton microscopy for dissecting cellular dynamics in arthritic inflammation and bone destruction. (2014)
  • Author(s): Kikuta J, Ishii M.
  • Journal Title: Methods in Molecular Biology Volume: 1142 Pages: 1-10
  • DOI: 10.1007/978-1-4939-0404-4_1
  • ISBN: 9781493904037, 9781493904044
• [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
  • 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
  • Peer Reviewed / Open Access
• [Journal Article] Dynamic Analysis of Histamine-Mediated Attenuation of Acetylcholine-Induced Sweating via GSK3β Activation. (2014)
  • Author(s): Matsui S, Murota H, Takahashi A, Yang L, Lee JB, Omiya K, Ohmi M, Kikuta J, Ishii M, Katayama I.
  • Journal Title: Journal of Investigative Dermatology Volume: 134 Issue: 2 Pages: 326-334
  • DOI: 10.1038/jid.2013.323
  • Peer Reviewed
• [Journal Article] Generation of colonic IgA-secreting cells in the cecal patch (2014)
  • Author(s): Masahata, K., Umemoto, E., Kayama, H., Kotani, M., Nakamura, S., Kurakawa, T., Kikuta, J., Gotoh, K., Motooka, D., Sato, S., Higuchi, T., Baba, Y., Kurosaki, T., Kinoshita, M., Shimada, Y., Kimura, T., Okumura, R., Takeda, A., Tajima, M., Yoshie, O., Fukuzawa, M., Kiyono, H., Fagarasan, S., Iida, T., Ishii, M., Takeda, K
  • Journal Title: Nature Comm Volume: 5 Issue: 1 Pages: 3704-3704
  • DOI: 10.1038/ncomms4704
  • Peer Reviewed / Open Access
• [Journal Article] Dynamic live imaging of bone: opening a new era with 'bone histodynametry'. (2013)
  • Author(s): Masaru Ishii
  • Journal Title: Journal of Bone and Mineral Metabolism Volume: in press Issue: 5 Pages: 507-511
  • DOI: 10.1007/s00774-013-0437-x
  • Peer Reviewed
• [Presentation] 蛍光生体イメージング技術による骨髄・免疫細胞の動態解析 (2014)
  • Author(s): 菊田順一
  • Organizer: 日本リウマチ学会第1回アニュアルベーシックコースレクチャー
  • Place of Presentation: アキバプラザ
  • Year and Date: 2014-10-25
  • Invited
• [Presentation] 生体二光子励起イメージングによる骨代謝ダイナミクスの動的解析 (2014)
  • Author(s): 菊田順一
  • Organizer: 第87回日本生化学会大会
  • Place of Presentation: 国立京都国際会館
  • Year and Date: 2014-10-16
  • Invited
• [Presentation] Dynamic analysis of short-term effects of bisphosphonates by using intravital two-photon microscopy. (2014)
  • Author(s): Junichi Kikuta, Mai Shirazaki, Masaru Ishii.
  • Organizer: The American Society for Bone and Mineral Research 2014 Annual Meeting
  • Place of Presentation: George R. Brown Convention Center, Houston, Texas, USA
  • Year and Date: 2014-09-13
• [Presentation] Intravital imaging of osteoclast dynamics by using multiphoton microscopy. (2014)
  • Author(s): Junichi Kikuta, Masayuki Furuya, Toshiyuki Kowada, Kazuya Kikuchi, Masaru Ishii.
  • Organizer: The 18th International Microscopy Congress
  • Place of Presentation: Prague Congress Centre, Prague, Czech Republic
  • Year and Date: 2014-09-10
• [Presentation] 生体多光子励起イメージングによる生きた細胞動態の解析 (2014)
  • Author(s): 菊田順一
  • Organizer: 第33回日本医用画像工学会
  • Place of Presentation: 東京慈恵会医科大学
  • Year and Date: 2014-07-26
  • Invited
• [Presentation] 2 光子励起顕微鏡を駆使した骨髄イメージング (2014)
  • Author(s): 菊田順一, 石井優
  • Organizer: 第32回日本骨代謝学会学術集会
  • Place of Presentation: 大阪国際会議場
  • Year and Date: 2014-07-25
  • Invited
• [Presentation] S1P-mediated osteoclast precursor monocyte migration is a critical point of control in antibone-resorptive action of active vitamin D.
  • Author(s): Kikuta J, Okiji F, Shirazaki M, Sakai S, Saito H, Ishii M.
  • Organizer: The American Society for Bone and Mineral Research 2013 Annual Meeting
  • Place of Presentation: Baltimore Convention Center, Baltimore, USA
• [Presentation] Dynamic in vivo imaging of vascular permeability in living bones by using intravital multiphoton microscopy.
  • Author(s): Kikuta J, Kaneko T, Ishii M.
  • Organizer: The 42th Annual Meeting of The Japanese Society for Immunology
  • Place of Presentation: Makuhari Messe, Chiba, Japan
• [Presentation] 生体多光子励起イメージングによる破骨細胞の動態解析
  • Author(s): 菊田順一
  • Organizer: 第14回運動器科学研究会
  • Place of Presentation: 汐留コンファレンスセンター、東京
  • Invited
• [Presentation] 骨のライブイメージングによる破骨細胞の動態解析
  • Author(s): 菊田順一
  • Organizer: 第7回骨・軟骨フロンティア
  • Place of Presentation: ベルサール八重洲、東京
  • Invited
• [Presentation] ライブイメージングによる骨髄・免疫細胞の動態解析
  • Author(s): 菊田順一
  • Organizer: 第16回骨代謝研究会
  • Place of Presentation: 慶應義塾大学医学部、東京
  • Invited
• [Presentation] Dynamic visualization of RANKL and Th17-mediated osteoclast function
  • Author(s): 菊田順一
  • Organizer: The 8th Bone Research Seminar
  • Place of Presentation: 東京コンファレンスセンター・品川、東京
  • Invited