2005 Fiscal Year Final Research Report Summary
The functional analysis of RANKL signaling in osteoclast for developing the agonist of SHP-1
| Project/Area Number |
16390530
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Functional basic dentistry
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| Research Institution | Tokyo Medical and Dental University |
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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)
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| 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)
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| Project Period (FY) |
2004 – 2005
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| Keywords | inflammation / immunology / osteoclast / SHP-1 / 3-dimensional surface measurement / proteome analysis / agonist design / evaluation for osteoclast function |
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| 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.
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[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.
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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
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[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.
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Journal Title
Nature Medicine 12(12)
Pages: 1410-1416
Description
「研究成果報告書概要(欧文)」より
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[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.
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Journal Title
Journal of Dental and Medical Sciences. 52(1)
Pages: 91-99
Description
「研究成果報告書概要(欧文)」より
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[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.
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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
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[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
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Journal Title
Nature Medicine 10
Pages: 617-624
Description
「研究成果報告書概要(欧文)」より
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