| Project/Area Number |
17K18256
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Orthopaedic surgery
General pharmacology
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| Research Institution | Kindai University |
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Principal Investigator |
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| Research Collaborator |
KAJI Hiroshi
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| Project Period (FY) |
2017-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2017: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | 閉経後骨粗鬆症 / 骨芽細胞 / 骨代謝 / 性差 / 骨粗鬆症 |
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| Outline of Final Research Achievements |
It has been suggested that factors other than sex hormones may also be involved in sex differences in osteoporosis and bone metabolism. In primary mouse osteoblasts, the differentiation and calcification were significantly lower in females than males. We performed the comprehensive gene expression analyses and Serpina3n was identified as a gene whose expression level is predominantly higher in females than males. While the reduced endogenous Serpina3n significantly enhanced osteoblast differentiation, enhanced Serpina3n significantly suppressed osteoblast differentiation in a mouse osteoblast cell line. In addition, Serpina3n did not affect the differentiation of mouse mesenchymal stem cell line into osteoblasts, but significantly suppressed calcification. From the above results, Serpina3n, which is predominantly expressed in female osteoblasts, suppresses the phenotype in differentiated osteoblasts. It would be partially able to explain sex differences in osteoblast phenotypes.
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| Academic Significance and Societal Importance of the Research Achievements |
骨粗鬆症は男性よりも女性に多くみられ、とくに閉経後骨粗鬆症は予後が悪く寝たきりの原因にもなり、医療費を圧迫している。そこで、我々は、雌由来骨芽細胞自身に性差を決める因子が存在するのではないかと考え、骨粗鬆症病態に重要な新しい性差に関連した因子としてSerpina3nを見出した。解析の結果、Serpina3nは骨芽細胞に対して、石灰化や骨芽細胞分化を負に作用する因子であることが明らかとなった。このSerpina3nが骨粗鬆症の病態形成に関与する可能性を示唆している。本研究成果により、Serpina3nをターゲットにした骨粗鬆症の新しい診断マーカーや治療薬の開発につながることが期待される。
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