| Project/Area Number |
16580065
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Applied microbiology
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| Research Institution | Chubu University |
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Principal Investigator |
WOO Je Tae Chubu University, College of Bioscience and Biotechnology, Professor, 応用生物学部, 教授 (20272693)
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| Co-Investigator(Kenkyū-buntansha) |
NAGAI Kazuo Chubu University, College of Bioscience and Biotechnology, Professor, 応用生物学部, 教授 (00011974)
OHNISHI Motoko Chubu University, College of Bioscience and Biotechnology, Assistant Professor, 応用生物学部, 助教授 (00312653)
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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 |
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 2005: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2004: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | destruxins / reveromycin A / compactin / bone resorption / osteoclast / osteoporosis / coptisine / berberine / 代謝産物 / アルカロイド / ベロマイシン / 細胞骨格 / 骨密度 / 微生物代謝産物 / 機能発現 |
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| Research Abstract |
In the present study, we determined action mode of reveromycin A (RMA), compactin (mevastatin) and destruxins in cell and molecular level on osteoclast differentiation and function, and screened new compounds from herbs that inhibit osteoclast differentiation. The target molecular of RMA is isoleusyl tRNA synthetase and the selective effect of RM-A on activated osteoclasts is due to the acidified microenviroment which is derived by activated osteoclast. RMA also inhibited the increase of bone resorption in ovariectomised mice. These results indicate that RMA could be a good candidate for a new anti-resorptive medicine with high specificity against activated osteoclasts. Mevastatin was shown to inhibit early differentiation of osteoclasts from their progenitor by decreasing geranylgeranyl pyrophosphate in the pathway of cholesterol synthesis. Geranylgeranyl transferase inhibitor inhibited the geranylgeranylation of small G-protein, suggesting that the geranylgeranylation of small G-protein is involved in the inhibitory effect of mevastatin on early differentiation of osteoclasts. Alkaloids, coptisine (from Coptidis Rhizoma) and berberine (Corydalis Tuber) were found to inhibit osteoclast differentiation. These compounds inhibited osteoclast differentiation by blocking the increase of expression of NFAT which is an essential transcription factor for osteoclast differentiation.
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