| Project/Area Number |
17H04050
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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 |
Pathological medical chemistry
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| Research Institution | The University of Tokyo (2019-2020)
Showa University (2017-2018) |
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Principal Investigator |
NEGISHI TAKAKO 東京大学, 医科学研究所, 特任准教授 (90451905)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥17,810,000 (Direct Cost: ¥13,700,000、Indirect Cost: ¥4,110,000)
Fiscal Year 2019: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2018: ¥6,760,000 (Direct Cost: ¥5,200,000、Indirect Cost: ¥1,560,000)
Fiscal Year 2017: ¥6,760,000 (Direct Cost: ¥5,200,000、Indirect Cost: ¥1,560,000)
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| Keywords | 骨代謝 / 破骨細胞 / 骨芽細胞 / 老化 / 認知症 / 骨粗鬆症 / 神経変性疾患 / 中枢神経 / 骨免疫学 / 骨代謝学 / 高次生体相互連関 |
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| Outline of Final Research Achievements |
We revealed that mice treated with the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) showed marked loss of the dopaminergic nerve in their substantia nigra, but did not exhibit spontaneous movement disorders such as those of Parkinson’s disease patients. Nevertheless, bone mass of these mice was significantly reduced. This suggested that the lack of dopaminergic nerves themselves may control bone metabolism. Osteoclastogenesis of cells derived from the bone marrow of these mice was normal, but the serum of these mice accelerated it. On the other hand, differentiation and mineralization of osteoblasts were suppressed by their serum and anti-prolactin antibody reversed this inhibitory effect, suggesting that prolactin in serum, which induced in dopaminergic degeneration mice suppressed osteoblastic bone formation. Thus, this study revealed that lack of dopamine results in bone loss by affecting bone homeostasis.
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| Academic Significance and Societal Importance of the Research Achievements |
既存の研究成果にも示されているように骨代謝と神経系が共通の因子で制御されている可能性は高い。本研究はそのような因子を同定することによって、骨粗鬆症と認知症といった高齢者の２大疾患を同時に制御できる治療戦略を開発することに繋がる可能性を持つ。本研究で明らかにしたパーキンソン病に付随する骨粗鬆症も、単に運動能の低下による廃用性骨粗鬆症として諦観するのではなく、積極的に骨量を維持する治療の重要性を提示することができた。
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