| Project/Area Number |
17K10916
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Orthopaedic surgery
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| Research Institution | Hirosaki University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
和田 簡一郎 弘前大学, 医学部附属病院, 講師 (20431447)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2019: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2017: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | 間葉系幹細胞 / 異所性骨化 / 脊柱靭帯 / エピジェネティクス / メカニカルストレス / DNAメチル化 / 生理活性物質 / スクリーニング / 脊柱靭帯骨化症 / 形質転換 / 天然生理活性物質 / 骨化抑制 / 細胞遊走 / SDF-1 / CXCR4 / コンドロモジュリン / 内軟骨性骨化 / 治療薬 |
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| Outline of Final Research Achievements |
We hypothesized that the pathogenesis of ossification of the spinal ligament is the acquisition of mesenchymal stem cells (MSCs) scattered in ligament tissue for osteogenic differentiation. In order to prove the hypothesis, we first constructed an MSC library, which is a research resource. Next, we considered that the mechanism of MSC transformation was methylation of genomic DNA, and performed genome-wide DNA methylation analysis.
We found that methylation levels of the genes of interest in the GWAS study were significantly altered between MSCs in patient tissues and normal MSCs. On the other hand, for the purpose of searching for seeds of therapeutic agents, a substance that suppresses calcification of MSCs was screened using a physiologically active substance library, and a plurality of drugs effective at very low concentrations were found.
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| Academic Significance and Societal Importance of the Research Achievements |
（学術的意義）現在の治療研究におけるトレンドの多施設研究で、研究資源を共通化することは極めて重要であり、今回間葉系幹細胞ライブラリーを構築したことは、研究の進展に果たす役割は大きい。またDNAメチル化のゲノムワイドの解析は、病因解明の新しいアプローチであり、得られた情報は薬物治療の重要なターゲットとなる可能性がある。
（社会的意義) 骨化抑制物質の探索は、治療薬のシーズとなる物質を見出す有力な方法である。今回非常に低濃度で間葉系幹細胞の石灰化を抑制する物質を複数個見いだせた。それを基に構造活性相関の研究を行えば、より強力で特異性の高い治療薬の開発につなげることが出来る。
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