Evidence map›Paper›PMID 36278281›Full record

ArticleThe EMBO journal2022

Hypoxia promotes osteogenesis by facilitating acetyl-CoA-mediated mitochondrial-nuclear communication.

Andromachi Pouikli, Monika Maleszewska, Swati Parekh, Ming Yang, Chrysa Nikopoulou, Juan Jose Bonfiglio, Constantine Mylonas, Tonantzi Sandoval, Anna-Lena Schumacher, Yvonne Hinze and 3 more

Open access · hybridAbstract read
In one paragraph

Article in The EMBO journal, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.

0numbers the graph read from it
0cells of the map it votes in
30citing papers in PubMed
2.9field-weighted citation impact, top 7% 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

30 citing papers in PubMed, 32 citations in OpenAlex.

  1. Bone organoids and mitochondrial reprogramming.Journal of orthopaedic translation · 2026
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  15. Mitochondria - the CEO of the cell.Journal of cell science · 2025
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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

13 authors at 2 institutions in 1 country.

Andromachi PouikliMax Planck Research Group "Chromatin and Ageing", Max Planck Institute for Biology of Ageing, Cologne, Germany.ORCID 0000-0003-1868-6875
Monika MaleszewskaMax Planck Research Group "Chromatin and Ageing", Max Planck Institute for Biology of Ageing, Cologne, Germany.
Swati ParekhMax Planck Research Group "Chromatin and Ageing", Max Planck Institute for Biology of Ageing, Cologne, Germany.
Ming YangCologne Excellence Cluster on Stress Responses in Ageing-Associated Diseases (CECAD), Cologne, Germany.ORCID 0000-0002-7735-7804
Chrysa NikopoulouMax Planck Research Group "Chromatin and Ageing", Max Planck Institute for Biology of Ageing, Cologne, Germany.ORCID 0000-0001-7982-7737
Juan Jose BonfiglioResearch Group "Proteomics and ADP-Ribosylation Signaling", Max Planck Institute for Biology of Ageing, Cologne, Germany.ORCID 0000-0001-7767-0799
Constantine MylonasMax Planck Research Group "Chromatin and Ageing", Max Planck Institute for Biology of Ageing, Cologne, Germany.
Tonantzi SandovalMax Planck Research Group "Chromatin and Ageing", Max Planck Institute for Biology of Ageing, Cologne, Germany.
Anna-Lena SchumacherFACS & Imaging Core Facility, Max Planck Institute for Biology of Ageing, Cologne, Germany.ORCID 0000-0001-7739-486X
Yvonne HinzeMetabolomics Core Facility, Max Planck Institute for Biology of Ageing, Cologne, Germany.ORCID 0000-0002-2966-9862
Ivan MaticCologne Excellence Cluster on Stress Responses in Ageing-Associated Diseases (CECAD), Cologne, Germany.
Christian FrezzaCologne Excellence Cluster on Stress Responses in Ageing-Associated Diseases (CECAD), Cologne, Germany.
Peter TessarzMax Planck Research Group "Chromatin and Ageing", Max Planck Institute for Biology of Ageing, Cologne, Germany.ORCID 0000-0002-6953-9835
Max Planck Institute for Biology of Ageing · DECologne Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases · DE

Funding

Cancer Research UK C51061/A27453Medical Research Council MC_UU_12022/6
6 · The paper itself

Abstract

Bone-derived mesenchymal stem cells (MSCs) reside in a hypoxic niche that maintains their differentiation potential. While hypoxia (low oxygen concentration) was reported to critically support stem cell function and osteogenesis, the molecular events triggering changes in stem cell fate decisions in response to normoxia (high oxygen concentration) remain elusive. Here, we study the impact of normoxia on mitochondrial-nuclear communication during stem cell differentiation. We show that normoxia-cultured murine MSCs undergo profound transcriptional alterations which cause irreversible osteogenesis defects. Mechanistically, high oxygen promotes chromatin compaction and histone hypo-acetylation, particularly on promoters and enhancers of osteogenic genes. Although normoxia induces metabolic rewiring resulting in elevated acetyl-CoA levels, histone hypo-acetylation occurs due to the trapping of acetyl-CoA inside mitochondria owing to decreased citrate carrier (CiC) activity. Restoring the cytosolic acetyl-CoA pool remodels the chromatin landscape and rescues the osteogenic defects. Collectively, our results demonstrate that the metabolism-chromatin-osteogenesis axis is perturbed upon exposure to high oxygen levels and identifies CiC as a novel, oxygen-sensitive regulator of the MSC function.

Indexed as

HistonesOsteogenesisAcetyl Coenzyme AAnimalsCell DifferentiationCells, CulturedChromatinHypoxiaMiceMitochondriaOxygenAcetyl Coenzyme AChromatinHistonesOxygenhistone acetylationhypoxiamesenchymal stem cellsmetabolismosteogenesis

Identifiers

PMID36278281
PMCPMC9713713
OpenAlexW4307178494

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.