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2023 Fiscal Year Final Research Report

Analysis of the novel osteoclastogenesis system induced by oral squamous cell carcinoma cells

Research Project

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Project/Area Number 20H03857
Research Category

Grant-in-Aid for Scientific Research (B)

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

Principal Investigator

Ikeda Tohru  東京医科歯科大学, 大学院医歯学総合研究科, 教授 (00211029)

Co-Investigator(Kenkyū-buntansha) 栢森 高  東京医科歯科大学, 大学院医歯学総合研究科, 講師 (10569841)
坂本 啓  東京医科歯科大学, 大学院医歯学総合研究科, 講師 (00302886)
Project Period (FY) 2020-04-01 – 2024-03-31
Keywords破骨細胞 / 口腔扁平上皮癌 / 破骨細胞前駆細胞 / RANKL / IL-1
Outline of Final Research Achievements

Previously, we discovered that cancer cells derived form human oral squamous cell carcinoma (OSCC) induced many osteoclasts when cultured with osteoclast precursor cells but not from untreated bone marrow-derived macrophages. Osteoclast precursor cells fail to differentiate into osteoclasts without further treatment of RANKL. We also found that the OSCC-induced osteoclastogenesis did not correlate with the expression of NFATc1 and the osteoclastogenesis was resistant to denosumab but inhibited with CBD. In this study, we found that IL-1, that is widely expressed in OSCC stimulated both RANKL-induced osteoclastogenesis and OSCC-induced osteoclastogenesis independently. Our study suggests that bone resorption caused by infiltration of OSCC cells is induced by both IL-1-stimulated physiological bone resorption and IL-1-stimulated OSCC induced-induced osteoclastogenesis.

Free Research Field

口腔病理学

Academic Significance and Societal Importance of the Research Achievements

口腔癌の進展によって起こる過剰な骨吸収が生理的骨吸収が単に亢進したものなのか、口腔癌細胞による独自の破骨細胞誘導機構が存在するのかについては全く不明であった。我々の一連の研究により、口腔扁平上皮癌は破骨細胞への分化が決定づけられているがそのままでは破骨細胞に分化が進まない破骨細胞前駆細胞を標的として強力に破骨細胞を誘導することが示されたが、今回の研修成果はさらに、癌細胞が発現するIL-1が生理的骨代謝に加え、癌細胞による破骨細胞誘導機構もともに促進することが、口腔扁平上皮癌による骨吸収のメカニズムであることを示した。この成果によって口腔癌による骨吸収機構の全容解明に大きな進展をもたらした。

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Published: 2025-01-30  

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