Evidence map›Paper›PMID 40722170›Full record

ArticleJournal of translational medicine2025

Chronic intermittent hypoxia impairs BM-MSC osteogenesis and long bone growth through regulating histone lactylation.

Fang Chen, Meizhen Gu, Hongming Xu, Shasha Zhou, Zilu Shen, Xiaoyan Li, Liangchao Dong, Pin Li

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of translational medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
–field-weighted citation impact
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

8 citing papers in PubMed.

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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

8 authors.

Fang Chen *Department of Otolaryngology-Head and Neck Surgery, Shanghai Children's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200062, China.
Meizhen Gu *Department of Otolaryngology-Head and Neck Surgery, Shanghai Children's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200062, China.
Hongming XuDepartment of Otolaryngology-Head and Neck Surgery, Shanghai Children's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200062, China.
Shasha ZhouDepartment of Endocrinology, Shanghai Children's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200062, China.
Zilu ShenDepartment of Otolaryngology-Head and Neck Surgery, Shanghai Children's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200062, China.
Xiaoyan LiDepartment of Otolaryngology-Head and Neck Surgery, Shanghai Children's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200062, China. lxyshchildren@163.com.
Liangchao DongDepartment of Orthopedics, Shanghai Children's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200062, China. alextung3399@163.com.
Pin LiDepartment of Endocrinology, Shanghai Children's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200062, China. lipin2019@126.com.

Funding

China International Medical Foundation z-2019-41-2201General Program of the National Natural Science Foundation of China 81871131General Program of the National Natural Science Foundation of China 82171121
6 · The paper itself

Abstract

backgroundChronic intermittent hypoxia (CIH) caused by OSA often results in serious complications. However, the adverse effects of CIH on bone growth and development are often overlooked.

methodsCIH intervention was conducted using an OxyCycler model A84 system for 8 h per day (from 8:00 a.m. to 4:00 p.m.) over a period of 4 weeks. Body and femur lengths were measured, and micro-CT, histological analysis, and ELISA were performed to evaluate femoral development. Metabolomic, single-cell transcriptomic, Western blot, and ChIP‒qPCR analyses were conducted to explore the potential mechanisms underlying CIH-induced inhibition of long bone growth. T0070907 was administered intraperitoneally (0.5 mg/kg) every two days to investigate its effect on long bone growth under CIH conditions.

resultsHere, we showed that CIH stimulation during long bone development significantly inhibited long bone growth. Multiomics analysis revealed that CIH induces anaerobic glycolysis in bone marrow mesenchymal stem cells (BM-MSCs), promotes adipogenic differentiation, and reduces their osteogenic differentiation capacity. Mechanistic studies demonstrated that CIH-induced lactate accumulation enhances lactylation at histone H3 lysine 18 (H3K18) on the PPARγ promoter in BM-MSCs, leading to the transcriptional activation of PPARγ and a consequent imbalance between the adipogenic and osteogenic differentiation of BM-MSCs. The PPARγ inhibitor T0070907 could partially rescue long bone developmental disorders induced by CIH.

conclusionsOur findings reveal an epigenetic mechanism underlying CIH-induced long bone dysplasia and highlight T0070907 as a promising targeted therapeutic agent.

Indexed as

Bone DevelopmentHistonesHypoxiaMesenchymal Stem CellsOsteogenesisAdipogenesisAnimalsCell DifferentiationChronic DiseaseFemurGlycolysisMaleMicePPAR gammaHistonesPPAR gammaBM-MSCsBone developmentChronic intermittent hypoxiaHistone lactylationPPARγ

Identifiers

PMID40722170
PMCPMC12306074

What Socratic 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 Socratic graph.