| 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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| Project Status |
Completed (Fiscal Year 2005)
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| 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)
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| Keywords | inflammation / 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 |
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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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