Evidence map›Paper›PMID 34661337›Full record

ArticleEMBO reports2021

Osteoclasts adapt to physioxia perturbation through DNA demethylation.

Keizo Nishikawa, Shigeto Seno, Toshitada Yoshihara, Ayako Narazaki, Yuki Sugiura, Reito Shimizu, Junichi Kikuta, Reiko Sakaguchi, Norio Suzuki, Norihiko Takeda and 12 more

Open access · bronzeAbstract read
In one paragraph

Article in EMBO reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
1.5field-weighted citation impact, top 18% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

18 citing papers in PubMed, 23 citations in OpenAlex.

  1. Exacerbation of inflammatory bone loss in TET2-driven clonal hematopoiesis.Journal of immunology (Baltimore, Md. : 1950) · 2026
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

22 authors at 11 institutions in 1 country.

Keizo NishikawaLaboratory of Cell Biology and Metabolic Biochemistry, Department of Medical Life Systems, Graduate School of Life and Medical Sciences, Doshisha University, Kyotanabe, Japan.ORCID 0000-0002-9725-1556
Shigeto SenoDepartment of Bioinformatic Engineering, Graduate School of Information Science and Technology, Osaka University, Osaka, Japan.ORCID 0000-0003-3861-6444
Toshitada YoshiharaDepartment of Chemistry and Chemical Biology, Gunma University, Kiryu, Japan.
Ayako NarazakiGraduate School of Medicine/Frontier Biosciences, Osaka University, Suita, Japan.
Yuki SugiuraDepartment of Biochemistry, Keio University, Tokyo, Japan.
Reito ShimizuLaboratory of Cell Biology and Metabolic Biochemistry, Department of Medical Life Systems, Graduate School of Life and Medical Sciences, Doshisha University, Kyotanabe, Japan.
Junichi KikutaDepartment of Immunology and Cell Biology, WPI-Immunology Frontier Research Center, Osaka University, Suita, Japan.
Reiko SakaguchiWPI-Research Initiative-Institute for Integrated Cell-Material Science, Kyoto University, Kyoto, Japan.
Norio SuzukiDivision of Oxygen Biology, Tohoku University Graduate School of Medicine, Sendai, Japan.
Norihiko TakedaDepartment of Cardiovascular Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Hiroaki SembaDepartment of Cardiovascular Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Masamichi YamamotoDepartment of Artificial Kidneys, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Daisuke OkuzakiSingle Cell Genomics, Human Immunology, WPI Immunology Frontier Research Center, Osaka University, Suita, Japan.ORCID 0000-0002-4552-783X
Daisuke MotookaGenome Information Research Center, Research Institute for Microbial Diseases, Osaka University, Suita, Japan.
Yasuhiro KobayashiInstitute for Oral Science, Matsumoto Dental University, Shiojiri, Japan.
Makoto SuematsuDepartment of Biochemistry, Keio University, Tokyo, Japan.
Haruhiko KosekiDevelopmental Genetics Group, Center for Integrative Medical Sciences, RIKEN, Yokohama, Japan.ORCID 0000-0001-8424-5854
Hideo MatsudaDepartment of Bioinformatic Engineering, Graduate School of Information Science and Technology, Osaka University, Osaka, Japan.ORCID 0000-0002-4701-3779
Masayuki YamamotoDepartment of Medical Biochemistry, Tohoku University Graduate School of Medicine, Sendai, Japan.ORCID 0000-0002-9073-9436
Seiji TobitaDepartment of Chemistry and Chemical Biology, Gunma University, Kiryu, Japan.
Yasuo MoriWPI-Research Initiative-Institute for Integrated Cell-Material Science, Kyoto University, Kyoto, Japan.ORCID 0000-0001-7180-1938
Masaru IshiiDepartment of Immunology and Cell Biology, WPI-Immunology Frontier Research Center, Osaka University, Suita, Japan.ORCID 0000-0002-4215-007X
The University of Osaka · JPTohoku University · JPUbe Frontier University · JPDoshisha University · JPGunma University · JPKeio University · JPKyoto University · JPCardiovascular Institute Hospital · JPMatsumoto Dental University · JPRIKEN Center for Integrative Medical Sciences · JPThe University of Tokyo · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

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.

Indexed as

DNA DemethylationOsteoclastsAnimalsCell DifferentiationCell HypoxiaHypoxiaMiceOxygenOxygenbone metabolismepigenetic regulationintravital imagingosteoclastoxygen

Identifiers

PMID34661337
PMCPMC8647016
OpenAlexW3205041972

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.