| Project/Area Number |
18K09126
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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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| Review Section |
Basic Section 56020:Orthopedics-related
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| Research Institution | University of Occupational and Environmental Health, Japan |
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Principal Investigator |
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2020: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | TRPVチャネル / DXA法 / マイクロCT / 初代骨髄細胞培養 / 骨形態計測 / 尾部懸垂 / TRPV / DXA / μCT / RT-PCR / microCT / 骨代謝 / メカニカルストレス |
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| Outline of Final Research Achievements |
In this study, the OXT system in the hypothalamo-neurohypophysial and hypothalamo-spinal pathway was surveyed using a rat neuropathic pain model induced by partial sciatic nerve ligation (PSL). In the present study, we used transgenic rats expressing an OXT-monomeric red fluorescent protein 1 (mRFP1) fusion gene. In a neuropathic pain model, mechanical allodynia was observed, and glial cell activation was also confirmed via immunohistochemistry. In this neuropathic pain model, a significant increase in the OXT-mRFP1 expression was observed in the PP, the SON, mPVN, and pPVN. Furthermore, OXT-mRFP1 granules with positive fluorescent reaction were remarkably increased in laminae I and II of the ipsilateral dorsal horn. Although the plasma concentrations of OXT did not significantly change, a significant increase of the mRNA levels of OXT and mRFP1 in the SON, mPVN, and pPVN were observed.
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| Academic Significance and Societal Importance of the Research Achievements |
近年骨粗鬆症が健康寿命を障害すると認識され骨粗鬆症の発症機序に基づいた新規治療薬が開発されている。非選択的陽イオンチャネルであるTRPV1およびTRPV4チャネルは破骨細胞と骨芽細胞に発現しこれらの分化に関与するが、TRPV1 KOやTRPV4 KOに加えて二重ノックアウト（DKO）マウスを用いて骨吸収系の抑制と骨形成系の亢進が同時に起こることを明らかにした。既存の治療薬のような骨吸収系の抑制や骨形成系の促進のみの薬剤と比較して、より強力な骨粗鬆症治療が可能となる新規創薬につながる研究で、意義のある研究であると考えられる。
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