2022 Fiscal Year Final Research Report

Functional and pathological analyses of inflammatory bone destruction disease by a novel Rab protein

Research Project

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Project/Area Number	20H03860
Research Category	Grant-in-Aid for Scientific Research (B)
Allocation Type	Single-year Grants
Section	一般
Review Section	Basic Section 57020:Oral pathobiological science-related
Research Institution	Nagasaki University
Principal Investigator	Tsukuba Takayuki 長崎大学, 医歯薬学総合研究科(歯学系), 教授 (30264055)
Co-Investigator(Kenkyū-buntansha)	坂井詠子長崎大学, 医歯薬学総合研究科(歯学系), 助教 (10176612) 山口優長崎大学, 医歯薬学総合研究科(歯学系), 助教 (50823308) 門脇知子長崎大学, 医歯薬学総合研究科(歯学系), 教授 (70336080)
Project Period (FY)	2020-04-01 – 2023-03-31
Keywords	炎症性骨破壊疾患 / 細胞内輸送 / 歯周病 / 関節リウマチ / Rab44
Outline of Final Research Achievements	Periodontal disease and rheumatoid arthritis are representative inflammatory bone destruction diseases, which are caused by dysregulation of osteoclasts and immune cells. Through our own research, we identified a novel gene, Rab44, that is expressed in osteoclasts and immune cells. However, the function of Rab44 in vivo is unknown. The purpose of this study is to elucidate the function of Rab44 in inflammatory bone destruction diseases. To this end, we used Rab44 knockout mice to model periodontal disease and rheumatoid arthritis, and compared the disease states of wild-type and Rab44-knockout mice. Based on this study, we will elucidate a new aspect of intracellular vesicle trafficking in immune cells and osteoclasts, leading to analysis of its role in inflammatory bone destruction diseases.
Free Research Field	歯科薬理学、細胞生物学
Academic Significance and Societal Importance of the Research Achievements	Rab44の研究は破骨細胞の多核化のメカニズムを膜輸送や小胞輸送という切り口から明らかにできる可能性があり、膜輸送と細胞の多核化・巨大化の関係性を明らかにできる可能性が含まれている。さらに骨代謝疾患の新しい病態の解明に繋がる可能性がある。本研究では破骨細胞や免疫系細胞にRab44が特異的に発現しているという我々の独自の知見を基盤にして歯周病や関節リウマチへの応用を視野に入れた研究を展開した。Rab44の分子基盤の解明は破骨細胞の骨吸収機構や免疫細胞でのRab44の解明にとって有益な情報となるだけでなく、新しい骨代謝治療薬あるいは歯周病治療薬への手掛かりになる可能性がある。