ID | 61276 |
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著者 |
Tran, Manh Tien
Department of Dental Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Okusha, Yuka
Department of Dental Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
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Feng, Yunxia
Department of Dental Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Morimatsu, Masatoshi
Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Wei, Penggong
Department of Dental Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Sogawa, Chiharu
Department of Dental Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
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Eguchi, Takanori
Department of Dental Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
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Kadowaki, Tomoko
Department of Frontier Oral Science, Graduate School of Biomedical Sciences, Nagasaki University
Sakai, Eiko
Department of Dental Pharmacology, Graduate School of Biomedical Sciences, Nagasaki University
Okamura, Hirohiko
Department of Oral Morphology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
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Naruse, Keiji
Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
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Tsukuba, Takayuki
Department of Dental Pharmacology, Graduate School of Biomedical Sciences, Nagasaki University
Okamoto, Kuniaki
Department of Dental Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
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抄録 | Rab11b, abundantly enriched in endocytic recycling compartments, is required for the establishment of the machinery of vesicle trafficking. Yet, no report has so far characterized the biological function of Rab11b in osteoclastogenesis. Using in vitro model of osteoclasts differentiated from murine macrophages like RAW-D cells or bone marrow-derived macrophages, we elucidated that Rab11b served as an inhibitory regulator of osteoclast differentiation sequentially via (i) abolishing surface abundance of RANK and c-Fms receptors; and (ii) attenuating nuclear factor of activated T-cells c1 (NFATc-1) upstream signaling cascades, following RANKL stimulation. Rab11b was localized in early and late endosomes, Golgi complex, and endoplasmic reticulum; moreover, its overexpression enlarged early and late endosomes. Upon inhibition of lysosomal function by a specific blocker, chloroquine (CLQ), we comprehensively clarified a novel function of lysosomes on mediating proteolytic degradation of c-Fms and RANK surface receptors, drastically ameliorated by Rab11b overexpression in RAW-D cell-derived osteoclasts. These findings highlight the key role of Rab11b as an inhibitor of osteoclastogenesis by directing the transport of c-Fms and RANK surface receptors to lysosomes for degradation via the axis of early endosomes-late endosomes-lysosomes, thereby contributing towards the systemic equilibrium of the bone resorption phase.
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キーワード | Rab11b
c-Fms
RANK
NFATc-1
osteoclasts
vesicular transport
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発行日 | 2020-12-08
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出版物タイトル |
International Journal of Molecular Sciences
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巻 | 21巻
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号 | 24号
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出版者 | MDPI
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開始ページ | 9352
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ISSN | 1422-0067
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NCID | AA12038549
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資料タイプ |
学術雑誌論文
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言語 |
英語
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OAI-PMH Set |
岡山大学
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著作権者 | © 2020 by the authors.
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論文のバージョン | publisher
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PubMed ID | |
DOI | |
Web of Science KeyUT | |
関連URL | isVersionOf https://doi.org/10.3390/ijms21249352
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ライセンス | http://creativecommons.org/licenses/by/4.0/
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助成機関名 |
日本学術振興会
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助成番号 | JP16K11863
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