Elucidation of the pathogenesis of bone and joint destruction and development of novel therapies

2023 Fiscal Year Final Research Report

• Project/Area Number: 21H02716
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 49030:Experimental pathology-related
• Research Institution: Osaka University
• Principal Investigator: Kikuta Junichi 大阪大学, 大学院医学系研究科, 招へい教員 (60710069)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 生体イメージング / オミクス解析 / 炎症性骨破壊 / 破骨細胞 / マクロファージ

Outline of Final Research Achievements

Osteoclasts are responsible for bone destruction. Under physiological conditions, osteoclasts exist in the bone marrow and play an important role in bone homeostasis. On the other hand, in pathological conditions such as arthritis, chronic inflammation in the synovium promotes osteoclast formation and induces bone destruction around joints. In this study, by means of intravital imaging techniques, we found that osteoclasts formed in two distinct localizations and microenvironments, bone marrow and inflamed synovium, were very different in terms of their movement and function. Furthermore, single-cell RNA sequencing analysis of cells isolated from inflamed synovial tissue revealed the regulatory mechanism of osteoclast differentiation involved in pathological bone destruction. These results would provide the basis for developing drugs that target pathological osteoclasts.

Free Research Field

免疫学、細胞生物学

Academic Significance and Societal Importance of the Research Achievements

本研究は、従来の研究手法では解析が困難であった生体の炎症関節内における破骨細胞の骨吸収動態を可視化することに成功するとともに、病的骨破壊に関わる破骨細胞の分化制御メカニズムを明らかにしたもので、国際的にも独自性が高く、学術的に大きな意義がある。最先端のライブイメージング技術とオミクス解析技術によって得られた基礎研究成果を臨床現場へ還元することにより、国内外の医療への貢献も期待され、その社会的意義も極めて大きい。