| Project/Area Number |
20590245
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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 |
General pharmacology
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| Research Institution | Hirosaki University |
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Principal Investigator |
FURUKAWA Kenichi Hirosaki University, 大学院・医学研究科, 准教授 (20165468)
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| Co-Investigator(Kenkyū-buntansha) |
SEYA Kazuhiko 弘前大学, 大学院・医学研究科, 助教 (40281919)
NUMASAWA Takuya 弘前大学, 大学院・医学研究科, 助教 (80396407)
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| Project Period (FY) |
2008 – 2010
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| Project Status |
Completed (Fiscal Year 2010)
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| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2010: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2009: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2008: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | 異所性骨化 / 脊柱靱帯 / 機械的ストレス / 薬物治療 / 脊柱靱帯骨化症 / 細胞外ATP受容体 / 幹細胞 / gremlin / BMP2 / P2Y1 / 過剰発現 / 骨化様式 / TSG-6 / 形質転換 / アルカリフォスファターゼ / メカニカルストレス / 細胞外ヌクレオチド受容体 / 遺伝子導入 / ATP |
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| Research Abstract |
To verify the hypothesis that P2Y1 expression causes ossification in the spinal ligaments, we forced expression of P2Y1 in spinal ligament cells obtained from OPLL and non-OPLL patients. The expression of mRNA and protein was investigated by quantitative real-time polymerase chain reaction and immunofluorescence staining, respectively. After transfection, bone morphogenetic protein-2 (BMP-2) and Sox9 mRNA expression was significantly increased in spinal ligament cells derived from OPLL patients compared with cells from non-OPLL patients 2 days after P2Y1 transient transfection. Immunofluorescence analysis showed that BMP-2 and P2Y1 expression was increased in OPLL patients only, while Sox9 expression was increased in OPLL and non-OPLL patients. MRS2279, a selective P2Y1 antagonist, blocked the upregulation of Sox9 and BMP-2 after forced expression of P2Y1. Furthermore, 4 days after transient transfection of P2Y1, mineralization was observed only in spinal ligament cells from OPLL patients. These results suggest that P2Y1 expression plays an important role in ectopic bone formation in the spinal ligaments of OPLL patients and that a drug which modulates the P2Y1 function will be a potential candidate for the drug in the therapy of OPLL.
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