Osteoclasts adapt to physioxia perturbation through DNA demethylation

Nishikawa, Keizo; Seno, Shigeto; Yoshihara, Toshitada; Narazaki, Ayako; Sugiura, Yuki; Shimizu, Reito; Kikuta, Junichi; Sakaguchi, Reiko; Suzuki, Norio; Takeda, Norihiko; Semba, Hiroaki; Yamamoto, Masamichi; Okuzaki, Daisuke; Motooka, Daisuke; Kobayashi, Yasuhiro; Suematsu, Makoto; Koseki, Haruhiko; Matsuda, Hideo; Yamamoto, Masayuki; Tobita, Seiji; Mori, Yasuo; Ishii, Masaru

doi:https://doi.org/10.15252/embr.202153035

Osteoclasts adapt to physioxia perturbation through DNA demethylation

Nishikawa, Keizo; Seno, Shigeto; Yoshihara, Toshitada et al.

EMBO Reports, 2021, 22(12), e53035

Number of Access:241（2025-04-24 13:29 Counts）

Identifier to cite or link to this item: https://hdl.handle.net/11094/93156

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Title	Osteoclasts adapt to physioxia perturbation through DNA demethylation
Creator	CreatorName Nishikawa, Keizo
	NRID 1000030432462 1000030432462 ORCID 0000-0003-3861-6444 0000-0003-3861-6444 researchmap permalink ssenoo ssenoo Scopus Author ID 57214748425 57214748425 CreatorName Seno, Shigeto
	NRID 1000010375561 1000010375561 CreatorName Yoshihara, Toshitada
	CreatorName Narazaki, Ayako
	NRID 1000030590202 1000030590202 CreatorName Sugiura, Yuki
	CreatorName Shimizu, Reito
	NRID 1000060710069 1000060710069 researchmap permalink jkikuta jkikuta Scopus Author ID 36637603800 36637603800 CreatorName Kikuta, Junichi
	NRID 1000080723197 1000080723197 CreatorName Sakaguchi, Reiko
	NRID 1000020447254 1000020447254 CreatorName Suzuki, Norio
	NRID 1000040422307 1000040422307 CreatorName Takeda, Norihiko
	NRID 1000080747923 1000080747923 CreatorName Semba, Hiroaki
	NRID 1000070423150 1000070423150 CreatorName Yamamoto, Masamichi
	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 1000010636830 1000010636830 researchmap permalink daisukem daisukem Scopus Author ID 35315737900 35315737900 CreatorName Motooka, Daisuke
	NRID 1000020264252 1000020264252 CreatorName Kobayashi, Yasuhiro
	NRID 1000000206385 1000000206385 CreatorName Suematsu, Makoto
	NRID 1000040225446 1000040225446 CreatorName Koseki, Haruhiko
	NRID 1000050183950 1000050183950 ORCID 0000-0002-4701-3779 0000-0002-4701-3779 researchmap permalink Hideo_Matsuda Hideo_Matsuda Scopus Author ID 35381793100 35381793100 CreatorName Matsuda, Hideo
	NRID 1000050166823 1000050166823 CreatorName Yamamoto, Masayuki
	NRID 1000030164007 1000030164007 CreatorName Tobita, Seiji
	NRID 1000080212265 1000080212265 CreatorName Mori, Yasuo
	NRID 1000010324758 1000010324758 researchmap permalink read0076684 read0076684 Scopus Author ID 35074093500 35074093500 CreatorName Ishii, Masaru
Subject	bone metabolism
	epigenetic regulation
	intravital imaging
	osteoclast
	oxygen
Description	Nishikawa K., Seno S., Yoshihara T., et al. Osteoclasts adapt to physioxia perturbation through DNA demethylation. EMBO Reports 22, e53035 (2021); https://doi.org/10.15252/embr.202153035.
Abstract	Oxygen plays an important role in diverse biological processes. However, since quantitation of the partial pressure of cellular oxygen in vivo is challenging, the extent of oxygen perturbation in situ and its cellular response remains underexplored. Using two-photon phosphorescence lifetime imaging microscopy, we determine the physiological range of oxygen tension in osteoclasts of live mice. We find that oxygen tension ranges from 17.4 to 36.4 mmHg, under hypoxic and normoxic conditions, respectively. Physiological normoxia thus corresponds to 5% and hypoxia to 2% oxygen in osteoclasts. Hypoxia in this range severely limits osteoclastogenesis, independent of energy metabolism and hypoxia-inducible factor activity. We observe that hypoxia decreases ten-eleven translocation (TET) activity. Tet2/3 cooperatively induces Prdm1 expression via oxygen-dependent DNA demethylation, which in turn activates NFATc1 required for osteoclastogenesis. Taken together, our results reveal that TET enzymes, acting as functional oxygen sensors, regulate osteoclastogenesis within the physiological range of oxygen tension, thus opening new avenues for research on in vivo response to oxygen perturbation.
Publisher	John Wiley and Sons Inc
Source Title	EMBO Reports
Volume (Issue)	22(12)
Page	e53035
Date of Issued	2021-12-06
Language	English
Handle URL	https://hdl.handle.net/11094/93156
PISSN	1469221X
Relation.isIdenticalTo	DOI (Publisher Version) https://doi.org/10.15252/embr.202153035
Access Rights	open access
CopyRight	This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
oaire:version	Version of Record
Category	学術雑誌論文 Journal Article

Resource Type	journal article
Local Type	Journal Article
DCMI Type	Text
DCTERMS.bibliographicCitation	EMBO Reports. 2021, 22(12), p. e53035
DC.title	Osteoclasts adapt to physioxia perturbation through DNA demethylation
DC.creator	Nishikawa, Keizo
	Seno, Shigeto
	Yoshihara, Toshitada
	Narazaki, Ayako
	Sugiura, Yuki
	Shimizu, Reito
	Kikuta, Junichi
	Sakaguchi, Reiko
	Suzuki, Norio
	Takeda, Norihiko
	Semba, Hiroaki
	Yamamoto, Masamichi
	Okuzaki, Daisuke
	Motooka, Daisuke
	Kobayashi, Yasuhiro
	Suematsu, Makoto
	Koseki, Haruhiko
	Matsuda, Hideo
	Yamamoto, Masayuki
	Tobita, Seiji
	Mori, Yasuo
	Ishii, Masaru
DC.publisher	John Wiley and Sons Inc
DC.language' scheme='DCTERMS.RFC1766	English
DC.type' scheme='DCTERMS.DCMIType	Text
DCTERMS.issued' scheme='DCTERMS.W3CDTF	2021-12-06
DC.identifier	https://doi.org/10.15252/embr.202153035
DC.subject	bone metabolism
	epigenetic regulation
	intravital imaging
	osteoclast
	oxygen
DC.description	Nishikawa K., Seno S., Yoshihara T., et al. Osteoclasts adapt to physioxia perturbation through DNA demethylation. EMBO Reports 22, e53035 (2021); https://doi.org/10.15252/embr.202153035.
DCTERMS.abstract	Oxygen plays an important role in diverse biological processes. However, since quantitation of the partial pressure of cellular oxygen in vivo is challenging, the extent of oxygen perturbation in situ and its cellular response remains underexplored. Using two-photon phosphorescence lifetime imaging microscopy, we determine the physiological range of oxygen tension in osteoclasts of live mice. We find that oxygen tension ranges from 17.4 to 36.4 mmHg, under hypoxic and normoxic conditions, respectively. Physiological normoxia thus corresponds to 5% and hypoxia to 2% oxygen in osteoclasts. Hypoxia in this range severely limits osteoclastogenesis, independent of energy metabolism and hypoxia-inducible factor activity. We observe that hypoxia decreases ten-eleven translocation (TET) activity. Tet2/3 cooperatively induces Prdm1 expression via oxygen-dependent DNA demethylation, which in turn activates NFATc1 required for osteoclastogenesis. Taken together, our results reveal that TET enzymes, acting as functional oxygen sensors, regulate osteoclastogenesis within the physiological range of oxygen tension, thus opening new avenues for research on in vivo response to oxygen perturbation.
DC.rights	This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
DC.format	93156
citation_title	Osteoclasts adapt to physioxia perturbation through DNA demethylation
citation_author	Nishikawa, Keizo
	Seno, Shigeto
	Yoshihara, Toshitada
	Narazaki, Ayako
	Sugiura, Yuki
	Shimizu, Reito
	Kikuta, Junichi
	Sakaguchi, Reiko
	Suzuki, Norio
	Takeda, Norihiko
	Semba, Hiroaki
	Yamamoto, Masamichi
	Okuzaki, Daisuke
	Motooka, Daisuke
	Kobayashi, Yasuhiro
	Suematsu, Makoto
	Koseki, Haruhiko
	Matsuda, Hideo
	Yamamoto, Masayuki
	Tobita, Seiji
	Mori, Yasuo
	Ishii, Masaru
citation_publisher	John Wiley and Sons Inc
citation_language	English
citation_date	2021-12-06
citation_journal_title	EMBO Reports
citation_volume	22
citation_issue	12
citation_firstpage	e53035
citation_doi	https://doi.org/10.15252/embr.202153035
citation_public_url	https://hdl.handle.net/11094/93156

Osteoclasts adapt to physioxia perturbation through DNA demethylation

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