Identification of a novel arthritis-associated osteoclast precursor macrophage regulated by FoxM1

Hasegawa, Tetsuo; Kikuta, Junichi; Sudo, Takao; Matsuura, Yoshinobu; Matsui, Takahiro; Simmons, Szandor; Ebina, Kosuke; Hirao, Makoto; Okuzaki, Daisuke; Yoshida, Yuichi; Hirao, Atsushi; Kalinichenko, Vladimir V.; Yamaoka, Kunihiro; Takeuchi, Tsutomu; Ishii, Masaru

doi:https://doi.org/10.1038/s41590-019-0526-7

Identification of a novel arthritis-associated osteoclast precursor macrophage regulated by FoxM1

Hasegawa, Tetsuo; Kikuta, Junichi; Sudo, Takao et al.

Nature Immunology, 2019, 20(12), 1631-1643

Number of Access:1,949（2025-08-17 12:53 Counts）

Identifier to cite or link to this item: https://hdl.handle.net/11094/93182

Link to primary information

File	Format	Terms of use	Size	Views	Date.Available	Description	information
NatImmunol_20_12_1631	pdf	None	1.57 MB	59	2023.11.24
Supplement_20_12_1631	pdf	None	2.23 MB	37	2023.11.24

Item Information

Output File Export EndNote Basic Export Mendeley

Title	Identification of a novel arthritis-associated osteoclast precursor macrophage regulated by FoxM1
Creator	NRID 1000030773048 1000030773048 CreatorName Hasegawa, Tetsuo
	NRID 1000060710069 1000060710069 researchmap permalink jkikuta jkikuta Scopus Author ID 36637603800 36637603800 CreatorName Kikuta, Junichi
	NRID 1000080631184 1000080631184 researchmap permalink kik kik Scopus Author ID 36497716100 36497716100 CreatorName Sudo, Takao
	CreatorName Matsuura, Yoshinobu
	NRID 1000050747037 1000050747037 ORCID 0000-0002-6753-1688 0000-0002-6753-1688 researchmap permalink takahiromatsui takahiromatsui Scopus Author ID 35176152500 35176152500 CreatorName Matsui, Takahiro
	NRID 1000060598176 1000060598176 CreatorName Simmons, Szandor
	NRID 1000070612076 1000070612076 researchmap permalink k-ebina k-ebina Scopus Author ID 8415453300 8415453300 ORCID 0000-0002-2426-1024 0000-0002-2426-1024 CreatorName Ebina, Kosuke
	Scopus Author ID 8883255100 8883255100 CreatorName Hirao, Makoto
	NRID 1000000346131 1000000346131 ORCID 0000-0002-4552-783X 0000-0002-4552-783X researchmap permalink read0092307 read0092307 Scopus Author ID 6506703054 6506703054 CreatorName Okuzaki, Daisuke
	NRID 1000030457014 1000030457014 CreatorName Yoshida, Yuichi
	NRID 1000090343350 1000090343350 CreatorName Hirao, Atsushi
	CreatorName Kalinichenko, Vladimir V.
	CreatorName Yamaoka, Kunihiro
	NRID 1000050179610 1000050179610 CreatorName Takeuchi, Tsutomu
	NRID 1000010324758 1000010324758 researchmap permalink read0076684 read0076684 Scopus Author ID 35074093500 35074093500 CreatorName Ishii, Masaru
Description	Hasegawa T., Kikuta J., Sudo T., et al. Identification of a novel arthritis-associated osteoclast precursor macrophage regulated by FoxM1. Nature Immunology 20, 1631 (2019); https://doi.org/10.1038/s41590-019-0526-7.
Abstract	Osteoclasts have a unique bone-destroying capacity, playing key roles in steady-state bone remodeling and arthritic bone erosion. Whether the osteoclasts in these different tissue settings arise from the same precursor states of monocytoid cells is presently unknown. Here, we show that osteoclasts in pannus originate exclusively from circulating bone marrow-derived cells and not from locally resident macrophages. We identify murine CX3CR1hiLy6CintF4/80+I-A+/I-E+ macrophages (termed here arthritis-associated osteoclastogenic macrophages (AtoMs)) as the osteoclast precursor-containing population in the inflamed synovium, comprising a subset distinct from conventional osteoclast precursors in homeostatic bone remodeling. Tamoxifen-inducible Foxm1 deletion suppressed the capacity of AtoMs to differentiate into osteoclasts in vitro and in vivo. Furthermore, synovial samples from human patients with rheumatoid arthritis contained CX3CR1+HLA-DRhiCD11c+CD80−CD86+ cells that corresponded to mouse AtoMs, and human osteoclastogenesis was inhibited by the FoxM1 inhibitor thiostrepton, constituting a potential target for rheumatoid arthritis treatment.
Publisher	Nature Research
Source Title	Nature Immunology
Volume (Issue)	20(12)
Page	1631-1643
Date of Issued	2019-12-01
Language	English
Handle URL	https://hdl.handle.net/11094/93182
PISSN	15292908
eISSN	15292916
Relation.isVersionOf	DOI (Publisher Version) https://doi.org/10.1038/s41590-019-0526-7
Access Rights	open access
CopyRight	© 2019, The Author(s), under exclusive licence to Springer Nature America, Inc.
oaire:version	Accepted Manuscript
Category	学術雑誌論文 Journal Article

Resource Type	journal article
Local Type	Journal Article
DCMI Type	Text
DCTERMS.bibliographicCitation	Nature Immunology. 2019, 20(12), p. 1631-1643
DC.title	Identification of a novel arthritis-associated osteoclast precursor macrophage regulated by FoxM1
DC.creator	Hasegawa, Tetsuo
	Kikuta, Junichi
	Sudo, Takao
	Matsuura, Yoshinobu
	Matsui, Takahiro
	Simmons, Szandor
	Ebina, Kosuke
	Hirao, Makoto
	Okuzaki, Daisuke
	Yoshida, Yuichi
	Hirao, Atsushi
	Kalinichenko, Vladimir V.
	Yamaoka, Kunihiro
	Takeuchi, Tsutomu
	Ishii, Masaru
DC.publisher	Nature Research
DC.language' scheme='DCTERMS.RFC1766	English
DC.type' scheme='DCTERMS.DCMIType	Text
DCTERMS.issued' scheme='DCTERMS.W3CDTF	2019-12-01
DC.identifier	https://doi.org/10.1038/s41590-019-0526-7
DC.description	Hasegawa T., Kikuta J., Sudo T., et al. Identification of a novel arthritis-associated osteoclast precursor macrophage regulated by FoxM1. Nature Immunology 20, 1631 (2019); https://doi.org/10.1038/s41590-019-0526-7.
DCTERMS.abstract	Osteoclasts have a unique bone-destroying capacity, playing key roles in steady-state bone remodeling and arthritic bone erosion. Whether the osteoclasts in these different tissue settings arise from the same precursor states of monocytoid cells is presently unknown. Here, we show that osteoclasts in pannus originate exclusively from circulating bone marrow-derived cells and not from locally resident macrophages. We identify murine CX3CR1hiLy6CintF4/80+I-A+/I-E+ macrophages (termed here arthritis-associated osteoclastogenic macrophages (AtoMs)) as the osteoclast precursor-containing population in the inflamed synovium, comprising a subset distinct from conventional osteoclast precursors in homeostatic bone remodeling. Tamoxifen-inducible Foxm1 deletion suppressed the capacity of AtoMs to differentiate into osteoclasts in vitro and in vivo. Furthermore, synovial samples from human patients with rheumatoid arthritis contained CX3CR1+HLA-DRhiCD11c+CD80−CD86+ cells that corresponded to mouse AtoMs, and human osteoclastogenesis was inhibited by the FoxM1 inhibitor thiostrepton, constituting a potential target for rheumatoid arthritis treatment.
DC.rights	© 2019, The Author(s), under exclusive licence to Springer Nature America, Inc.
DC.format	93182
citation_title	Identification of a novel arthritis-associated osteoclast precursor macrophage regulated by FoxM1
citation_author	Hasegawa, Tetsuo
	Kikuta, Junichi
	Sudo, Takao
	Matsuura, Yoshinobu
	Matsui, Takahiro
	Simmons, Szandor
	Ebina, Kosuke
	Hirao, Makoto
	Okuzaki, Daisuke
	Yoshida, Yuichi
	Hirao, Atsushi
	Kalinichenko, Vladimir V.
	Yamaoka, Kunihiro
	Takeuchi, Tsutomu
	Ishii, Masaru
citation_publisher	Nature Research
citation_language	English
citation_date	2019-12-01
citation_journal_title	Nature Immunology
citation_volume	20
citation_issue	12
citation_firstpage	1631
citation_lastpage	1643
citation_doi	https://doi.org/10.1038/s41590-019-0526-7
citation_public_url	https://hdl.handle.net/11094/93182

Identification of a novel arthritis-associated osteoclast precursor macrophage regulated by FoxM1

Link to primary information

Item Information

Show details