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

2022 Fiscal Year Final Research Report

• Project/Area Number: 18K09532
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 57020:Oral pathobiological science-related
• Research Institution: Tokyo 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
• Keywords: CX3CL1 / 破骨細胞前駆細胞 / 細胞内カルシウム濃度 / 骨芽細胞

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.

Free Research Field

口腔外科学

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。