Identification and control of pathogenic osteoclasts

2023 Fiscal Year Final Research Report

• Project/Area Number: 19H05657
• Research Category: Grant-in-Aid for Scientific Research (S)
• Allocation Type: Single-year Grants
• Review Section: Broad Section I
• Research Institution: Osaka University
• Principal Investigator: Ishii Masaru 大阪大学, 大学院生命機能研究科, 教授 (10324758)
• Co-Investigator(Kenkyū-buntansha): 蛯名 耕介 大阪大学, 大学院医学系研究科, 准教授 (70612076)
• Project Period (FY): 2019-06-26 – 2024-03-31
• Keywords: 関節リウマチ / 炎症性骨破壊 / マクロファージ / 生体イメージング

Outline of Final Research Achievements

In this study, we demonstrated that pathogenic osteoclasts, which are different from those maintaining normal bone metabolism, are formed in the arthritic joints, by means of our originally developed intravital imaging system accompanied with single cell analysis, and we succeeded in identifying an arthritic osteoclastogenic macrophage (AtoM) and another pathogenic macrophage AM1, which can induce AtoM in local inflammatory loci. We also showed that a transcription factor FoxM1 is important for the induction of AtoM, and we could also identify human AtoM by analyzing human samples. These results lead to the development of new therapies that can specifically inhibit pathological bone destruction caused by arthritis without affecting normal bone homeostasis.

Free Research Field

免疫学、リウマチ学

Academic Significance and Societal Importance of the Research Achievements

破骨細胞は一種類ではなく、正常の骨代謝を担う「善玉」と病的骨破壊を起こす「悪玉」が存在することが明らかになったことで、「悪玉」だけを選択的かつ強力に抑制する治療の開発につながり、その社会的意義は大きい。また病理組織における特徴的な病原性マクロファージの同定は、組織におけるマクロファージの多様性の解明につながり、関節腔以外にも肺や肝臓など多くの組織・臓器における多様な病原性マクロファージの同定につながる学術的意義がもたらされた。