| Project/Area Number |
18K19649
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| Research Category |
Grant-in-Aid for Challenging Research (Exploratory)
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| Allocation Type | Multi-year Fund |
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| Review Section |
Medium-sized Section 57:Oral science and related fields
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| Research Institution | Hokkaido University |
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Principal Investigator |
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| Project Period (FY) |
2018-06-29 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
Fiscal Year 2019: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
Fiscal Year 2018: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
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| Keywords | 骨粗鬆症 / 慢性疼痛 / PTH / 神経 / 骨格痛 / 口腔顔面痛 / 骨 / 骨格性疼痛 / 口腔顔面 / 疼痛 / シグナル / 創薬 |
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| Outline of Final Research Achievements |
This study investigated the antinociceptive effect of TPTD mainly on primary sensory neurons in ovariectomized (OVX) rats. Osteoprosis-induced pain behavior was partially recovered by TPTD. Consistently, the number and size of spinal microglial cells were significantly increased in the OVX rats, while TPTD treatment significantly reduced the number but not size of these cells. RNA sequencing-based bioinformatics of the dorsal root ganglia (DRG) demonstrated that changes in neuro-protective and inflammatory genes were involved in the pharmacological effect of TPTD. Most neurons in the DRG expressed substantial levels of parathyroid hormone 1 receptor. TPTD treatment of the cultured DRG-derived neuronal cells reduced the cAMP level and augmented the intracellular calcium level as the concentration increased. These findings suggest that TPTD targets neuronal cells as well as bone cells to exert its pharmacological action.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究は、これまで臨床的に報告されていたPTH製剤による疼痛軽減効果を、分子細胞生物学的に解明した。さらに、副甲状腺ホルモンであるPTHの標的細胞として神経細胞が同定されたことは、まさに教科書を書き換える発見である。本研究の発展により、ロコモティブシンドロームに対する治療選択肢の拡大や、新たな疼痛治療薬開発に繋がることが期待される。
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