Mechanisms of Inflammatory Osteoclast Formation Mediated by Inflammatory and Necrotic Cell Factors and Extracellular Matrix Interactions

2023 Fiscal Year Final Research Report

• Project/Area Number: 20K09412
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 56020:Orthopedics-related
• Research Institution: Yamaguchi University
• Principal Investigator: ASAGIRI Masataka 山口大学, 大学院医学系研究科, 教授 (20372435)
• Project Period (FY): 2020-04-01 – 2024-03-31
• Keywords: 細胞外マトリクス / 関節リウマチ / 歯周病 / 糖尿病 / 組織破壊 / 組織再構築 / 持続炎症 / 免疫学

Outline of Final Research Achievements

This study aimed to elucidate the mechanisms of dysregulated bone metabolism under inflammatory conditions. We initially focused on osteoclasts and gained insights into their differentiation and activation. We also identified that inflammatory cytokines and methylglyoxal (MGO), a metabolite derived from hyperglycemia, disrupt bone metabolism. Building upon these findings, we revealed that MGO impairs osteoblast function and inhibits extracellular matrix mineralization, leading to decreased bone formation. These findings contribute to our understanding of the pathogenesis of osteoporosis, rheumatoid arthritis, and diabetes-related bone disorders, and may pave the way for novel therapeutic strategies. These results have been disseminated through conference presentations and manuscript submissions (some in preparation).

Free Research Field

免疫薬理学・実験病理学

Academic Significance and Societal Importance of the Research Achievements

本研究成果は、加齢や疾患に伴う骨・関節破壊のメカニズム解明、特に炎症環境下での骨関連細胞の形成過程に着目する点で学術的に新規性が高い。従来着目されてこなかった細胞外マトリクスの役割や、炎症・死細胞因子の特性解明を通じ、骨・関節疾患の病態理解を深めることが期待される。さらに、本研究から得られた知見は、既存薬が無効な炎症性骨疾患に対する新たな治療標的の発見や、薬剤の効果を高める併用療法の開発に繋がり、骨関節疾患患者のQOL向上や医療費削減に貢献する社会的意義も大きい。