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ATG4-LC3経路の阻害は破骨細胞の成熟を抑制した

日浦, 史隆 HIURA, Fumitaka ヒウラ, フミタカ 九州大学

2023.03.20

概要

九州大学学術情報リポジトリ
Kyushu University Institutional Repository

Inhibition of the ATG4-LC3 pathway suppressed
osteoclast maturation
日浦, 史隆

https://hdl.handle.net/2324/6787518
出版情報:Kyushu University, 2022, 博士(歯学), 課程博士
バージョン:
権利関係:© 2022 Elsevier Inc. All rights reserved.

(様式3)





論 文 名



日浦 史隆

: Inhibition of the ATG4-LC3 pathway suppressed osteoclast maturation
(ATG4-LC3経路 の阻害 は破骨 細 胞の成 熟を抑 制した)









:甲











オートファジーは、細胞が自身の一部を分解し、分解された細胞成分を再利用する
非選択的な作用である。オートファジー関連遺伝子(ATG)ファミリーの中で、ATG4 タン
パク質は、オートファゴソームの成熟に不可欠な微小管関連タンパク質 1 軽鎖 3(LC3)
にホスファチジルエタノールアミン(PE)を付加する過程で重要な役割を担っている。オ
ートファジーは破骨細胞の骨吸収に関与することが示されているが、ATG4/LC3 の骨吸
収における役割は不明である。マクロファージコロニー刺激因子(M-CSF)存在下、
receptor activator of NF-kB ligand(RANKL)処理 1 時間前にマウス骨髄細胞を
ATG4B の特異的阻害剤 NSC185058(NSC)で処理すると、NSC は破骨細胞形成を用
量依存的に阻害した。破骨細胞分化の後期に NSC を添加すると、多核化が抑制され、
Dc-stamp、Mmp9、Ctsk などの成熟破骨細胞マーカーの遺伝子発現が減少した。また、
NSC は成熟破骨細胞におけるアクチンリング形成と吸収窩の形成を抑制した。8 週齢
の野生型雄マウス上顎右側第二臼歯を絹糸で結紮した歯周炎モデルマウスに NSC ま
たは PBS を投与すると、NSC 投与群で破骨細胞数の減少による歯槽骨の吸収が抑制
された。以上の結果より、ATG4B/LC3 は破骨細胞の成熟過程に重要で、ATG4B/LC3
の阻害は歯周病による骨吸収に対する新たな治療戦略になることが示唆された。

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Authorship contributions

Fumitaka Hiura: Investigation, Formal analysis, Writing e

original draft, Writing - review & editing. Yuko Kawabata: Supervision, Writing - review & editing. Tsukasa Aoki: Investigation,

review & editing. Akiko Mizokami: Supervision, Writing - review

& editing. Eijiro Jimi: Funding acquisition, Conceptualization,

Writing - review & editing.

Funding

This study was supported by a research grant for the OBT

Research Center from the Kyushu University (to E.J.) and from the

Research Fellowship for Young Scientists (19J21202 to F.H.).

Declaration of competing interest

The authors have declared no conflicts of interest.

Acknowledgments

The authors thank Mr. Hiroshi Otowa for his technical assistance

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