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Mechanism of CX3CL1-mediated invasion of osteoclast progenitor cells through the osteoblast layer in inflammatory diseases.

Research Project

Project/Area Number 18K09532
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 57020:Oral pathobiological science-related
Research InstitutionTokyo Medical and Dental University

Principal Investigator

Tachikawa Noriko  東京医科歯科大学, 大学院医歯学総合研究科, 准教授 (70236537)

Co-Investigator(Kenkyū-buntansha) 中浜 健一  東京医科歯科大学, 大学院医歯学総合研究科, 准教授 (60281515)
Project Period (FY) 2018-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
KeywordsCX3CL1 / 破骨細胞前駆細胞 / 細胞内カルシウム濃度 / 骨芽細胞 / cAMP濃度 / HeLa細胞 / RANKL / M-CSF
Outline of Final Research Achievements

We tried to detect the RANK-RANKL interaction using split luciferase fusion proteins. RANK and RANKL cording regions were fused with LgBiT and SmBiT of the luciferase respectively. The LgBiT-RANK expressed HeLa cells were co-cultured with the RANKL-SmBiT expressing HeLa cells in the presence of luciferase substrate. This co-culture experiment showed the RANK-RANKL interaction between HeLa cells, which was canceled in the presence of an anti-RANKL neutral antibody. This is an important finding that will enable the detection of RANK-RANKL binding in living cells and can be applied to the screening of drugs for osteoporosis.

Academic Significance and Societal Importance of the Research Achievements

顎口腔外科領域において顎骨壊死や癌細胞の骨転移は診療を行う上で最も解決しなければならない問題である。これらに関わっているのがRANK-RANKL結合から始まる細胞内情報伝達機構である。本研究において、生細胞におけるRANK-RANKL結合を世界で初めて示すことができた。さらに、本実験系を薬剤のスクリーニング系に応用することで新規な低分子の骨粗鬆症薬や癌転移抑制剤の開発につなげたい。

Report

(6 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • 2020 Research-status Report
  • 2019 Research-status Report
  • 2018 Research-status Report

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Published: 2018-04-23   Modified: 2024-01-30  

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