Evidence map›Paper›PMID 38809508›Full record

ArticleAging2024

Trimethylamine-N-oxide promotes osteoclast differentiation and oxidative stress by activating NF-κB pathway.

Yangyang Zhao, Chizhen Wang, Fei Qiu, Jing Liu, Yujuan Xie, Zhengkun Lin, Jianquan He, Jian Chen

Abstract read
In one paragraph

Article in Aging, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed, 1 pooled it
–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

22 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Gut microbiome and bone health: update on mechanisms, clinical correlations, and possible treatment strategies.Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA · 2025
    Pooled it
  2. Review
  3. Gut microbes · 2026
    Article
  4. Review
  5. Article
  6. Review
  7. Review
  8. Article
  9. Review
  10. Review
  11. Trimethylamine-N-oxide: the microbial cue in immune-mediated disorders.Trends in endocrinology and metabolism: TEM · 2026
    Review
  12. Article
  13. Review
  14. Article
  15. Article
  16. Article
  17. Review
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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.

Yangyang ZhaoDepartment of Rehabilitation, Zhongshan Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China.
Chizhen WangSchool of Medicine, Xiamen University, Xiamen, China.
Fei QiuDepartment of Rehabilitation, Zhongshan Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China.
Jing LiuSchool of Medicine, Xiamen University, Xiamen, China.
Yujuan XieDepartment of Rehabilitation, Zhongshan Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China.
Zhengkun LinDepartment of Rehabilitation, Zhongshan Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China.
Jianquan HeDepartment of Rehabilitation, Zhongshan Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China.
Jian ChenDepartment of Rehabilitation, Zhongshan Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundSenile osteoporosis may be caused by an imbalance in intestinal flora and oxidative stress. Trimethylamine-N-oxide (TMAO), a metabolite of dietary choline dependent on gut microbes, has been found to be significantly increased in osteoporosis. However, the role of TMAO in bone loss during osteoporosis remains poorly understood. In this study, we examined the impact of TMAO on osteoclast differentiation and bone resorption in an

methodsOsteoclast differentiation was induced by incubating RAW 264.7 cells in the presence of Receptor Activator for Nuclear Factor-κB Ligand (RANKL) and macrophage-stimulating factor (M-CSF). Flow cytometry, TRAP staining assay, CCK-8, and ELISA were employed to investigate the impact of TMAO on osteoclast differentiation and bone resorption activity

resultsOur findings demonstrate that TMAO enhances RANKL and M-CSF-induced osteoclast formation and bone resorption in a dose-dependent manner. Mechanistically, TMAO triggers the upregulation of the NF-κB pathway and osteoclast-related genes (NFATc1, c-Fos, NF-κB p65, Traf6, and Cathepsin K). Furthermore, TMAO markedly elevated the levels of oxidative stress and inflammatory factors.

conclusionsIn conclusion, TMAO enhances RANKL and M-CSF-induced osteoclast differentiation and inflammation in RAW 264.7 cells by activating the NF-κB signaling pathway. These findings offer a new rationale for further academic and clinical research on osteoporosis treatment.

Indexed as

Cell DifferentiationMethylaminesNF-kappa BOsteoclastsOxidative StressRANK LigandSignal TransductionAnimalsBone ResorptionMacrophage Colony-Stimulating FactorMiceRAW 264.7 CellsMacrophage Colony-Stimulating FactorMethylaminesNF-kappa BRANK LigandTnfsf11 protein, mousetrimethyloxamineinflammationNF-κBosteoclastreactive oxygen speciestrimethylamine-N-oxide

Identifiers

PMID38809508
PMCPMC11164488

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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.