• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

The functional analysis of RANKL signaling in osteoclast for developing the agonist of SHP-1

Research Project

Project/Area Number 16390530
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Functional basic dentistry
Research InstitutionTokyo Medical and Dental University

Principal Investigator

AOKI Kazuhiro  Tokyo Medical and Dental University, Graduate School, Assistant Professor, 大学院医歯学総合研究科, 助手 (40272603)

Co-Investigator(Kenkyū-buntansha) HARUMIYA Satoru  Tokyo Medical and Dental University, Faculty of Dentistry, Technician(Faculty Staff), 歯学部, 教務職員 (50301792)
SHIMOKAWA Hitoyata  Tokyo Medical and Dental University, Graduate school, Associate Professor, 大学院医歯学総合研究科, 助教授 (80014257)
NAKAGAWA Atsushi  Osaka University, Research Center for Structural and Fuctional Proteomics, Professor, 蛋白質研究所, 教授 (20188890)
ISHIGURO Masaji  Suntory Institute for Bioorganic Research, Director, 部長研究員 (10280687)
Project Period (FY) 2004 – 2005
Project Status Completed (Fiscal Year 2005)
Budget Amount *help
¥14,500,000 (Direct Cost: ¥14,500,000)
Fiscal Year 2005: ¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 2004: ¥12,500,000 (Direct Cost: ¥12,500,000)
Keywordsinflammation / immunology / osteoclast / SHP-1 / 3-dimensional surface measurement / proteome analysis / agonist design / evaluation for osteoclast function / 骨吸収能 / 骨吸収機能 / 3D形状計測 / 骨吸収能評価法
Research Abstract

The SHP-1 is the phosphatase and the reduction of its phosphatase activity leads to the significant increase of bone resorption activity of osteoclasts, suggesting that SHP-1 works as a negative regulator of osteoclast activity. Here we have planned to develop the inhibitor of osteoclast activity by designing the agonist, which would increase the interaction between SHP-1 and its binding protein. We had already found SHP-1 binding proteins by using the MALDI-TOF system in SHP-1-transfected 293Tcells. The binding proteins were La binding protein, ribosome protein L4, protein tyrosine phosphatase 1c, KRT19. These proteins were, however, the fragments of SHP-1 or non-specific binding proteins, thereby we could not get in the next step such as screening for the functional proteins by using siRNA and develop the agonist of SHP-1. To solve this problem, we have also tried to find the SHP-1 binding protein by using the GST pull-down assay in murine macrophage cell line, RAW 264.7, but we could not identify the proteins. In spite of these results, it should be mentioned that the new system for measuring osteoclast activity has been established by using the device for measuring the 3-dimensional surface morphology which was purchased from this grant for screening the functional proteins which affects osteoclast activity. Previously the assessment of osteoclast activity was obtained by measuring 2-dimentinal area of the resorption pits, and the evaluation of the osteoclast activity has not been certain. In the near future, this evaluation system would be a powerful tool for the drug development.

Report

(3 results)
  • 2005 Annual Research Report   Final Research Report Summary
  • 2004 Annual Research Report
  • Research Products

    (44 results)

All 2006 2005 2004 Other

All Journal Article (44 results)

  • [Journal Article] A TNF receptor loop peptide mimic blocks RANK ligand-induced signaling, bone resorption, and bone loss2006

    • Author(s)
      Aoki K et al.
    • Journal Title

      Journal of Clinical Investigation 116(6)

      Pages: 1525-1534

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Regulation of osteoclast differentiation and function by the CaMK-CREB pathway.2006

    • Author(s)
      Sato K et al.
    • Journal Title

      Nature Medicine 12(12)

      Pages: 1410-1416

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Bovine deciduous dentine is more susceptible to osteoclastic resorption than permanent dentine : results of quantitative analyses.2006

    • Author(s)
      Varghese BJ, Aoki K et al.
    • Journal Title

      Journal of Bone and Mineral Metabolism. 24(3)

      Pages: 248-254

    • NAID

      10018194082

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Three-Dimensional Measurements of Bone Resorption Lacunae Reveal Inhibition of Osteoclast Activity by TNF-α Antagonist In Vitro.2006

    • Author(s)
      Satito H et al.
    • Journal Title

      Dentistry in Japan. 42

      Pages: 35-37

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Amelioration of bone loss in collagen-induced arthritis by neutralizing anti-RANKL monoclonal antibody.2006

    • Author(s)
      Kamijo S et al.
    • Journal Title

      Biochemical and Biophysical Research Communications. 347(1)

      Pages: 124-132

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] A tumor necrosis factor-α antagonist inhibits inflammatory bone resorption induced by Porphyromonas gingivalis infection in mice.2006

    • Author(s)
      Suzuki Y, Aoki K et al.
    • Journal Title

      Journal of Periodontal Research 41(2)

      Pages: 81-91

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Regional distinctions in cortical bone mineral density measured by pQCT can predict alterations in material property at the tibial diaphysis of the Cynomolgus monkey.2006

    • Author(s)
      Nonaka K et al.
    • Journal Title

      Bone 38(2)

      Pages: 265-272

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] A TNF receptor loop peptide mimic blocks RANK ligand-induced signaling, bone resorption, and bone loss.2006

    • Author(s)
      Aoki K, Saito H, Itzstein C, Ishiguro M, Shibata T, Blanque R, Mian AH, Takahashi M, Suzuki Y, Yoshimatsu M, Yamaguchi A, Deprez P, Mollat P, Murali R, Ohya K, Horne WC, Baron R.
    • Journal Title

      The Journal of Clinical Investigation. 116(6)

      Pages: 1525-1534

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Regional distinctions in cortical bone mineral density measured by pQCT can predict alterations in material property at the tibial diaphysis of the Cynomolgus monkey.2006

    • Author(s)
      Nonaka K, Fukuda S, Aoki K, Yoshida T, Ohya K.
    • Journal Title

      Bone. 38(2)

      Pages: 265-272

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] A tumor necrosis factor-α antagonist inhibits inflammatory bone resorption induced by Porphyromonas gingivalis infection in mice.2006

    • Author(s)
      Suzuki Y, Aoki K, Saito H, Umeda M, Nitta H, Baron R, Ohya K.
    • Journal Title

      Journal of Periodontal Research. 41(2)

      Pages: 81-91

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Three-Dimensional Measurements of Bone Resorption Lacunae Reveal Inhibition of Osteoclast Activity by TNF-α Antagonist In Vitro.2006

    • Author(s)
      Saito H, Soysa N, Alles N, Aoki K, Ohya K.
    • Journal Title

      Dentistry in Japan. 42

      Pages: 35-37

    • NAID

      10019595335

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Bovine deciduous dentine is more susceptible to osteoclasic resorption than permanent dentine : results of quantitative analyses.2006

    • Author(s)
      Varghese BJ, Aoki K, Shimokawa H, Ohya K, Takagi Y.
    • Journal Title

      Journal of Bone and Mineral Metabolism. 24(3)

      Pages: 248-254

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Amelioration of bone loss in collagen-induced arthritis by neutralizing anti-RANKL monoclonal antibody.2006

    • Author(s)
      Kamijo S, Nakajima A, Ikeda K, Aoki K, Ohya K, Akiba H, Yagita H, Okumura K.
    • Journal Title

      Biochemical and Biophysical Research Communications. 347(1)

      Pages: 124-132

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Regulation of osteoclast differentiation and function by the CaMK-CREB pathway.2006

    • Author(s)
      Sato K, Suematsu A, Nakashima T, Takemoto-Kimura S, Aoki K, Morishita Y, Asahara H, Ohya K, Yamaguchi A, Takai T, Kodama T, Chatila TA, Bito H, Takayanagi H.
    • Journal Title

      Nature Medicine 12(12)

      Pages: 1410-1416

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] A TNF-_□ antagonist inhibits inflammatory bone resorption induced by Porphyromonas gingivbalis infection in mice.2006

    • Author(s)
      Suzuki Y, Aoki K, Saito H, Umeda M, Nitta H, Baron R, Ohya K
    • Journal Title

      Journal of Periodontal Research 41

      Pages: 81-91

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Regional distinctions in cortical bone mineral density measured by pQCT can predict alterations in material property at the tibial diaphysis of the Cynomolgus monkey.2006

    • Author(s)
      Kiichi Nonaka, Satoshi Fukuda, Kazuhiro Aoki, Takashi Yoshida, Keiichi Ohya
    • Journal Title

      Bone 38

      Pages: 265-272

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Subcutaneous Injections of a TNF-α Antagonistic Peptide Inhibit Both Inflammation and Bone Resorption in Collagen-Induced Murine Arthritis.2005

    • Author(s)
      Kojima T, Aoki K et al.
    • Journal Title

      Journal of Dental and Medical Sciences. 52(1):

      Pages: 91-99

    • NAID

      110001065281

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Inhibition of RANKL-induced Osteoclastogenesis by (-)-DHMEQ, a Novel NF-kB Inhibitor, Through Downregulation of NFATcl.2005

    • Author(s)
      Takatsuna H et al.
    • Journal Title

      Journal of Bone and Mineral Research. 20(4)

      Pages: 653-662

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Effectiveness of Extracted-teeth as Bone Substitute : Application to Parietal Bone Defects in Rabbits.2005

    • Author(s)
      Tint K et al.
    • Journal Title

      Journal of Oral Tissue Engineering. 3(1)

      Pages: 7-16

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] 関節リウマチの最新動向-RANK/RANKLシグナル伝達阻害剤2005

    • Author(s)
      青木和広, 大谷啓一
    • Journal Title

      日本臨床 63(9)

      Pages: 1620-1626

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Subcutaneous Injections of a TNF-α Antagonistic Peptide Inhibit Both Inflammation and Bone Resorption in Collagen-Induced Murine Arthritis.2005

    • Author(s)
      Kojima T, Aoki K, Nonaka K, Saito H, Azuma M, Iwai, Varghese BJ, Yoshimasu H, Baron R, Ohya K, Amagasa T.
    • Journal Title

      Journal of Dental and Medical Sciences. 52(1)

      Pages: 91-99

    • NAID

      110001065281

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Inhibition of RANKL-induced Osteoclastogenesis by (-)-DHMEQ, a Novel NF-kB Inhibitor, Through Downregulation of NFATc1.2005

    • Author(s)
      Takatsuna H, Asagiri M, Kubota T, Oka K, Osada T, Sugiyama C, Saito H, Aoki K, Ohya K, Takayanagi H, Umezawa K.
    • Journal Title

      Journal of Bone and Mineral Research. 20(4)

      Pages: 653-662

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Effectiveness of Extracted-teeth as Bone Substitute : Application to Parietal Bone Defects in Rabbits.2005

    • Author(s)
      Tint K, Kondo H, Kuroda S, Fujimori T, Aoki K, Ohya K, Kasugai S.
    • Journal Title

      Journal of Oral Tissue Engineering. 3(1)

      Pages: 7-16

    • NAID

      110006263673

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] RANKL/RANK signaling-inhibitor2005

    • Author(s)
      K Aoki, K.Ohya
    • Journal Title

      Nippon Rinshou(Japanese Review article) 63(9)

      Pages: 1620-1626

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Subcutaneous Injections of a TNF-_□ Antagonistic Peptide Inhibit Both Inflammation and Bone Resorption in Collagen-Induced Murine Arthritis.2005

    • Author(s)
      T.Kojima, K.Aoki, K.Nonaka, H.Saito, M.Azuma, H.Iwai, B.J.BVarghese, H.Yoshimasu, R.Baron, K.Ohya, T.Amagasa
    • Journal Title

      Journal of Dental and Medical Sciences 52(1)

      Pages: 91-99

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Inhibition of RANKL-induced Osteoclastogenesis by (-)-DHMEQ, a Novel NF-kB Inhibitor, Through Downregulation of NFATcl.2005

    • Author(s)
      H.Takatsuna, M.Asagiri, T.Kubota, Ko.Oka, T.Osada, C.Sugiyama, H.Saito, K.Aoki, K.Ohya, H.Takayanagi, K.Umezawa
    • Journal Title

      Journal of Bone and Mineral Research 20(4)

      Pages: 653-662

    • Related Report
      2005 Annual Research Report
  • [Journal Article] RANKL/RANKシグナル伝達阻害剤.2005

    • Author(s)
      青木和広, 大谷啓一
    • Journal Title

      日本臨床 63(9)

      Pages: 1620-1626

    • Related Report
      2005 Annual Research Report
  • [Journal Article] The deficiency of immunoregulatory receptor PD-1 causes mild osteopetrosis.2004

    • Author(s)
      K.Nagahama, K.Aoki et al.
    • Journal Title

      Bone 35:

      Pages: 1059-1068

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Appearance of electron-dense segments : indication of possible conformation changes of pre-mineralizing collagen fibrils in the osteoid rat bones.2004

    • Author(s)
      Y.Asawa, K.Aoki et al.
    • Journal Title

      Journal of Electron Microscopy 53(4):

      Pages: 423-433

    • NAID

      10014037216

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Selective inhibition of NF-κB blocks osteoclastogenesis and prevents inflammatory bone destruction in vivo.2004

    • Author(s)
      E.Jimi, K.Aoki et al.
    • Journal Title

      Nature Medicine 10

      Pages: 617-624

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] 免疫細胞の骨代謝への関与2004

    • Author(s)
      青木和広, 大谷啓一, 長濱浩平
    • Journal Title

      整形・災害外科 47(6)

      Pages: 722-723

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Selective inhibition of NF-κB blocks osteoclastogenesis and prevents inflammatory bone destruction in vivo.2004

    • Author(s)
      E.Jimi, K.Aoki, H.Saito, F.D'Acquisto, M.J.May, I.Nakamura, T.Sudo, T.Kojima, F.Okamoto, H.Fukushima, K.Okabe, K.Ohya, S.Ghosh
    • Journal Title

      Nature Medicine 10

      Pages: 617-624

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] The deficiency of immunoregulatory receptor PD-1 causes mild osteopetrosis.2004

    • Author(s)
      K.Nagahama, K.Aoki, K.Nonaka, H.Saito, M.Takahashi, B.J.Varghese, H.Shimokawa, M.Azuma, K.Ohya, K.Ohyama
    • Journal Title

      Bone 35

      Pages: 1059-1068

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Appearance of electron-dense segments : indication of possible conformation changes of pre-mineralizing collagen fibrils in the osteoid rat bones.2004

    • Author(s)
      Y.Asawa, K.Aoki, K.Ohya, H.Ohshima, Y.Takano
    • Journal Title

      Journal of Electron Microscopy 53(4)

      Pages: 423-433

    • NAID

      10014037216

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Involvement of immune cells in the bone metabolism.2004

    • Author(s)
      K.Aoki, K.Ohya, K.Nagahama
    • Journal Title

      Orhtopaedic Surgery and Traumatology(Japanese Review article) 47(6)

      Pages: 722-723

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Selective inhibition of NF-kB blocks osteoclastogenesis and prevents inflammatory bone destruction in vivo.2004

    • Author(s)
      Jimi E, Aoki K, Saito H, D'Acquisto F, May MJ, Nakamura I, Sudo T, Kojima T, Okamoto F, Fukushima H, Okabe K, Ohya K, Ghosh S
    • Journal Title

      Nature Medicine 10(6)

      Pages: 617-624

    • Related Report
      2004 Annual Research Report
  • [Journal Article] A simple murine model for immobilization osteopenia.2004

    • Author(s)
      Damrongrungruang T, Kuroda S, Kondo H, Aoki K, Ohya K, Kasugai S
    • Journal Title

      Clinical Orthopaedics and Related Research 425

      Pages: 244-251

    • Related Report
      2004 Annual Research Report
  • [Journal Article] The deficiency of immunoregulatory receptor PD-1 causes mild osteopetrosis.2004

    • Author(s)
      Nagahama K, Aoki K, Nonaka K, Saito H, Takahashi M, Varghese BJ, Shimokawa H, Azuma M, Ohya K, Ohyama K
    • Journal Title

      Bone 35

      Pages: 1059-1068

    • Related Report
      2004 Annual Research Report
  • [Journal Article] 免疫系細胞の骨代謝への関与2004

    • Author(s)
      青木和広, 大谷啓一, 長濱浩平
    • Journal Title

      整形・災害外科(Orthopaedic Surgery and Traumatology) 47・6

      Pages: 722-723

    • Related Report
      2004 Annual Research Report
  • [Journal Article] A Tumor Necrosis Factor Receptor Loop Peptide Mimic Inhibits Bone Destruction to the Same Extent as Anti-Tumor Necrosis Factor Monoclonal Antibody in Murine Collagen-Induced Arthritis.

    • Author(s)
      Satito H et al.
    • Journal Title

      Arthritis and Rheumatism (in press)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Structure-base designed anti-TNFα peptide inhibits bone destruction in a same extent as anti-TNF monoclonal antibody in murine collagen-induced arthritis.

    • Author(s)
      Saito H, Kojima T, Takahashi M, Horne WC, Baron R, Amagasa T, Ohya K, Aoki K.
    • Journal Title

      Arthritis and Rheumatism (in press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Effectiveness of Extracted-teeth as Bone Substitute : Application to Parietal Bone Defects in Rabbits.

    • Author(s)
      K.Tint, H.Kondo, S.Kuroda, T.Fujimoro, K.Aoki, K.Ohya, S.Kasugai
    • Journal Title

      Journal of Oral Tissue Engineering (In Press)

    • NAID

      110006263673

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Bovine deciduous dentine is more susceptible to osteoclasic resorption than permanent dentine : results from quantitative analyses.

    • Author(s)
      Varghese BJ, Aoki K, Shimokawa H, Ohya K, Takagi Y
    • Journal Title

      Journal of Bone and Mineral Metabolism (In Press)

    • Related Report
      2005 Annual Research Report
  • [Journal Article] A Peptice Mimicking a TNF Receptor Loop Blocks RANKL-induced Signaling, Bone Resorption and Bone Loss.

    • Author(s)
      K.Aoki, H.Saito, C.Itzstein, M.Ishiguro et al.
    • Journal Title

      Journal of Clinical Investigation (In Press)

    • Related Report
      2005 Annual Research Report

URL: 

Published: 2004-04-01   Modified: 2016-04-21  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi