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

アクセス数:401件（2025-05-18 12:45 集計）

固定URL: https://hdl.handle.net/11094/93156

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タイトル	Osteoclasts adapt to physioxia perturbation through DNA demethylation
著者	著者名 Nishikawa, Keizo
	NRID 1000030432462 1000030432462 ORCID 0000-0003-3861-6444 0000-0003-3861-6444 researchmap permalink ssenoo ssenoo Scopus Author ID 57214748425 57214748425 著者名 Seno, Shigeto
	NRID 1000010375561 1000010375561 著者名 Yoshihara, Toshitada
	著者名 Narazaki, Ayako
	NRID 1000030590202 1000030590202 著者名 Sugiura, Yuki
	著者名 Shimizu, Reito
	NRID 1000060710069 1000060710069 researchmap permalink jkikuta jkikuta Scopus Author ID 36637603800 36637603800 著者名 Kikuta, Junichi
	NRID 1000080723197 1000080723197 著者名 Sakaguchi, Reiko
	NRID 1000020447254 1000020447254 著者名 Suzuki, Norio
	NRID 1000040422307 1000040422307 著者名 Takeda, Norihiko
	NRID 1000080747923 1000080747923 著者名 Semba, Hiroaki
	NRID 1000070423150 1000070423150 著者名 Yamamoto, Masamichi
	NRID 1000000346131 1000000346131 ORCID 0000-0002-4552-783X 0000-0002-4552-783X researchmap permalink read0092307 read0092307 Scopus Author ID 6506703054 6506703054 著者名 Okuzaki, Daisuke
	NRID 1000010636830 1000010636830 researchmap permalink daisukem daisukem Scopus Author ID 35315737900 35315737900 著者名 Motooka, Daisuke
	NRID 1000020264252 1000020264252 著者名 Kobayashi, Yasuhiro
	NRID 1000000206385 1000000206385 著者名 Suematsu, Makoto
	NRID 1000040225446 1000040225446 著者名 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 著者名 Matsuda, Hideo
	NRID 1000050166823 1000050166823 著者名 Yamamoto, Masayuki
	NRID 1000030164007 1000030164007 著者名 Tobita, Seiji
	NRID 1000080212265 1000080212265 著者名 Mori, Yasuo
	NRID 1000010324758 1000010324758 researchmap permalink read0076684 read0076684 Scopus Author ID 35074093500 35074093500 著者名 Ishii, Masaru
キーワード等	bone metabolism
	epigenetic regulation
	intravital imaging
	osteoclast
	oxygen
内容	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.
抄録	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.
出版者	John Wiley and Sons Inc
収録物名	EMBO Reports
巻(号)	22(12)
ページ	e53035
刊行年月	2021-12-06
言語	英語
ハンドルURL	https://hdl.handle.net/11094/93156
PISSN	1469221X
関連情報 (isIdenticalTo)	DOI (出版社版) https://doi.org/10.15252/embr.202153035
アクセス権	open access
権利情報	This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
出版タイプ	Version of Record
カテゴリ	学術雑誌論文 Journal Article

論文詳細を表示

資源タイプ	学術雑誌論文
ローカル資源タイプ	学術雑誌論文
DCMI資源タイプ	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	英語
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	英語
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