Osteoclasts adapt to physioxia perturbation through DNA demethylation.


Journal

EMBO reports
ISSN: 1469-3178
Titre abrégé: EMBO Rep
Pays: England
ID NLM: 100963049

Informations de publication

Date de publication:
06 12 2021
Historique:
revised: 03 09 2021
received: 09 04 2021
accepted: 16 09 2021
pubmed: 19 10 2021
medline: 15 3 2022
entrez: 18 10 2021
Statut: ppublish

Résumé

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.

Identifiants

pubmed: 34661337
doi: 10.15252/embr.202153035
pmc: PMC8647016
doi:

Substances chimiques

Oxygen S88TT14065

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

e53035

Informations de copyright

© 2021 The Authors. Published under the terms of the CC BY NC ND 4.0 license.

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Auteurs

Keizo Nishikawa (K)

Laboratory of Cell Biology and Metabolic Biochemistry, Department of Medical Life Systems, Graduate School of Life and Medical Sciences, Doshisha University, Kyotanabe, Japan.
Department of Immunology and Cell Biology, WPI-Immunology Frontier Research Center, Osaka University, Suita, Japan.
Graduate School of Medicine/Frontier Biosciences, Osaka University, Suita, Japan.

Shigeto Seno (S)

Department of Bioinformatic Engineering, Graduate School of Information Science and Technology, Osaka University, Osaka, Japan.

Toshitada Yoshihara (T)

Department of Chemistry and Chemical Biology, Gunma University, Kiryu, Japan.

Ayako Narazaki (A)

Graduate School of Medicine/Frontier Biosciences, Osaka University, Suita, Japan.

Yuki Sugiura (Y)

Department of Biochemistry, Keio University, Tokyo, Japan.

Reito Shimizu (R)

Laboratory of Cell Biology and Metabolic Biochemistry, Department of Medical Life Systems, Graduate School of Life and Medical Sciences, Doshisha University, Kyotanabe, Japan.

Junichi Kikuta (J)

Department of Immunology and Cell Biology, WPI-Immunology Frontier Research Center, Osaka University, Suita, Japan.
Graduate School of Medicine/Frontier Biosciences, Osaka University, Suita, Japan.
Laboratory of Bioimaging and Drug Discovery, National Institutes of Biomedical Innovation, Health and Nutrition, Ibaraki, Japan.

Reiko Sakaguchi (R)

WPI-Research Initiative-Institute for Integrated Cell-Material Science, Kyoto University, Kyoto, Japan.
Department of Synthetic Chemistry and Biological Chemistry, Graduate School of Engineering, Kyoto University, Kyoto, Japan.

Norio Suzuki (N)

Division of Oxygen Biology, Tohoku University Graduate School of Medicine, Sendai, Japan.

Norihiko Takeda (N)

Department of Cardiovascular Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.

Hiroaki Semba (H)

Department of Cardiovascular Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Department of Cardiovascular Medicine/Basic Research, The Cardiovascular Institute, Tokyo, Japan.

Masamichi Yamamoto (M)

Department of Artificial Kidneys, Graduate School of Medicine, Kyoto University, Kyoto, Japan.

Daisuke Okuzaki (D)

Single Cell Genomics, Human Immunology, WPI Immunology Frontier Research Center, Osaka University, Suita, Japan.

Daisuke Motooka (D)

Genome Information Research Center, Research Institute for Microbial Diseases, Osaka University, Suita, Japan.

Yasuhiro Kobayashi (Y)

Institute for Oral Science, Matsumoto Dental University, Shiojiri, Japan.

Makoto Suematsu (M)

Department of Biochemistry, Keio University, Tokyo, Japan.

Haruhiko Koseki (H)

Developmental Genetics Group, Center for Integrative Medical Sciences, RIKEN, Yokohama, Japan.

Hideo Matsuda (H)

Department of Bioinformatic Engineering, Graduate School of Information Science and Technology, Osaka University, Osaka, Japan.

Masayuki Yamamoto (M)

Department of Medical Biochemistry, Tohoku University Graduate School of Medicine, Sendai, Japan.

Seiji Tobita (S)

Department of Chemistry and Chemical Biology, Gunma University, Kiryu, Japan.

Yasuo Mori (Y)

WPI-Research Initiative-Institute for Integrated Cell-Material Science, Kyoto University, Kyoto, Japan.
Department of Synthetic Chemistry and Biological Chemistry, Graduate School of Engineering, Kyoto University, Kyoto, Japan.

Masaru Ishii (M)

Department of Immunology and Cell Biology, WPI-Immunology Frontier Research Center, Osaka University, Suita, Japan.
Graduate School of Medicine/Frontier Biosciences, Osaka University, Suita, Japan.
Laboratory of Bioimaging and Drug Discovery, National Institutes of Biomedical Innovation, Health and Nutrition, Ibaraki, Japan.

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