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Effect of toxic substances on bone remodeling -bone forming and bone resorption-

Research Project

Project/Area Number 16K09224
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Legal medicine
Research InstitutionNagoya City University (2017-2018)
St. Marianna University School of Medicine (2016)

Principal Investigator

Kanno Sanae  名古屋市立大学, 大学院医学研究科, 講師 (50391090)

Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Fiscal Year 2018: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Keywords骨芽細胞 / 依存性薬物 / 骨リモデリング / 分化 / 細胞内蓄積 / 骨形成 / MC3T3-E1 / コカイン / 石灰化 / 骨芽細胞の分化 / 覚せい剤 / アルカリホスファターゼ / 薬毒物 / 破骨細胞
Outline of Final Research Achievements

It has been reported that the chronic exposure to cocaine can lead to an adverse effect on skeletal development and caused to accumulation of cocaine in bone in rat experiment. However, the accumulation mechanisms of abused drugs, such as methamphetamine (MAP) or cocaine, in the bone have not been well documented. MC3T3-E1 cells, a mouse osteoblast-like cell line, can induce osteoblastic differentiation and mineralization. In this study, we investigated the effect of cocaine or methamphetamine (MAP) on cellular proliferation, osteoblastic differentiation and mineralization using MC3T3-E1 cells. These results indicate that chronic exposure to cocaine or MAP might have an adverse effect on bone development. Furthermore, to examine whether cellular accumulations of MAP and its main metabolite, amphetamine (AP), and cocaine and benzoylecgonine (BE), and are changed by mineralization, we compared their concentrations in the cells between with and without mineralization by LC-MS/MS.

Academic Significance and Societal Importance of the Research Achievements

本研究の結果は、依存性薬物の使用による骨リモデリングのアンバランスを引き起こす可能性があることを示した。慢性的な使用により依存性薬物が骨に蓄積する可能性も示唆された。これらの結果は、慢性的な使用による生体への悪影響の懸念を高めるものあり、大きな社会問題となっている依存性薬物の使用に警鐘を鳴らす、貴重なデータが得られたと考えられる。しかし、本研究ではまだ依存性薬物として広く使用されている2薬物だけである上に、分化条件下、未分化条件下での細胞への薬物蓄積には両薬物間で一貫性が認められなかった。今後、さらに多くの薬物を対象とした詳細な研究が必要である。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (3 results)

All 2019 2018 2017

All Presentation (3 results) (of which Int'l Joint Research: 1 results)

  • [Presentation] Cellular accumulation of cocaine following osteoblastic differentiation in MC3T3-E1 cells2019

    • Author(s)
      Kanno S., Otaki J., Kato H., Fukuta M., Nakamura Y., Horita T., Aoki Y.
    • Organizer
      Society of Toxicology
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] コカインが骨芽細胞様細胞MC3T3-E1の分化に及ぼす影響2018

    • Author(s)
      菅野 さな枝、大瀧 純、加藤 秀章、福田 真未子、堀田 哲也、中村 昌美、青木 康博
    • Organizer
      日本法中毒学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 骨芽細胞分化に伴うメタンフェタミンの細胞内蓄積と分化指標への影響2017

    • Author(s)
      1.菅野 さな枝, 千葉 正悦, 呂 彩子, 鷺 盛久, 井川 亨, 大出 透乃, 向井 敏二
    • Organizer
      第101年次日本法医学会
    • Related Report
      2017 Research-status Report

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Published: 2016-04-21   Modified: 2020-03-30  

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