Development of novel methods for evaluating RA pathogenesis and activity

• Project/Area Number: 25253070
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Collagenous pathology/Allergology
• Research Institution: Osaka University
• Principal Investigator: ISHII Masaru 大阪大学, 生命機能研究科, 教授 (10324758)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥44,980,000 (Direct Cost: ¥34,600,000、Indirect Cost: ¥10,380,000); Fiscal Year 2015: ¥13,910,000 (Direct Cost: ¥10,700,000、Indirect Cost: ¥3,210,000); Fiscal Year 2014: ¥13,910,000 (Direct Cost: ¥10,700,000、Indirect Cost: ¥3,210,000); Fiscal Year 2013: ¥17,160,000 (Direct Cost: ¥13,200,000、Indirect Cost: ¥3,960,000)
• Keywords: 関節リウマチ / イメージング / 関節炎 / 細胞動態 / 免疫・炎症 / 骨破壊 / 骨髄環境 / 免疫 / 炎症 / 細胞・組織 / シグナル伝達 / 医療・福祉 / トランスレーショナルリサーチ

Outline of Final Research Achievements

In this study, by using an advanced intravital imaging technology in our hand, we have elucidated the mode of cellular dynamics of different immune and inflammatory cells in arthritic joints. In addition, we have focused on the in vivo pharmacological actions of various biological agents used in clinic, and propose a new line of drug differentiation and development for rheumatic diseases.

Research Products

• [Int'l Joint Research] Yale University of Medicine(米国)
• [Journal Article] Real-time intravital imaging of pH variation associated with cell osteoclast activity and motility using designed small molecular probe. (2016)
  • Author(s): Maeda et al.,
  • Journal Title: Nature Chem. Biol. Volume: in press
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Intercellular communication between keratinocytes and fibroblasts induces local osteoclast differentiation: a mechanism underlying cholesteatoma-induced bone destruction. (2016)
  • Author(s): Iwamoto et al.,
  • Journal Title: Mol. Cell Biol. Volume: published online
  • 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
  • Peer Reviewed / Acknowledgement Compliant
• [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
  • 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
  • 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] 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 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] 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
  • Peer Reviewed
• [Presentation] Intravital multiphoton imaging revealing immune cell dynamics in inflammation and bone destruction in vivo. (2015)
  • Author(s): Masaru Ishii
  • Organizer: Japan-Germany Cancer Workshop
  • Place of Presentation: Berlin, Germany
  • Year and Date: 2015-11-15 – 2015-11-16
  • 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
  • Invited
• [Presentation] S1P-mediated control of bone cell dynamics visualized by intra-vital microscopy (2014)
  • Author(s): Masaru Ishii
  • Organizer: Gordon Research Conference
  • Place of Presentation: Ventura, CA (USA)
  • 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)
  • Invited
• [Remarks] 大阪大学生命機能研究科／医学系研究科 免疫細胞生物学教室
  • URL: http://www.icb.med.osaka-u.ac.jp/
• [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/