Evidence map›Paper›PMID 41120907›Full record

ArticleMolecular medicine (Cambridge, Mass.)2025

The YAP1/GPX4 axis alleviates osteoporosis by affecting ferroptosis in osteoblasts.

Mingsi Deng, Yong Zhou, Gengyan Liu, Ruimin Tang, Liangrong Hu, Jia Luo, Zhipeng Tang, Liangjian Chen, Zhengguang Wang

Abstract read
In one paragraph

Article in Molecular medicine (Cambridge, Mass.), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. Review
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

9 authors.

Mingsi Deng *Department of Stomatology, The Third Xiangya Hospital of Central South University, 138 Tongzipo Road, Yuelu District, Changsha City, Hunan Province, P.R. China.
Yong Zhou *Department of Spinal Surgery, The Third Xiangya Hospital of Central South University, 138 Tongzipo Road, Yuelu District, Changsha City, Hunan Province, 410013, P.R. China.
Gengyan LiuDepartment of Orthopedics, The Third Xiangya Hospital, Central South University, Changsha City, 410013, Hunan Province, P.R. China.
Ruimin TangDepartment of Stomatology, The Third Xiangya Hospital of Central South University, 138 Tongzipo Road, Yuelu District, Changsha City, Hunan Province, P.R. China.
Liangrong HuDepartment I of Orthopedics, Wugang Light Textile Orthopedic Hospital, Wugang City, Hunan Province, 422400, P.R. China.
Jia LuoChangsha Blood Center, Changsha City, Hunan Province, 410000, P.R. China.
Zhipeng TangJinshi Hospital of Traditional Chinese Medicine, Changde City, Hunan Province, 415400, P.R. China.
Liangjian ChenDepartment of Stomatology, The Third Xiangya Hospital of Central South University, 138 Tongzipo Road, Yuelu District, Changsha City, Hunan Province, P.R. China.
Zhengguang WangDepartment of Spinal Surgery, The Third Xiangya Hospital of Central South University, 138 Tongzipo Road, Yuelu District, Changsha City, Hunan Province, 410013, P.R. China. wangzhengguang0208@163.com.

Funding

Changsha Natural Science Foundation kq2403181Hunan Natural Science Foundation 2024JJ95529Hunan Natural Science Foundation Medical and Health Industry Joint Fund 2024JJ9533
6 · The paper itself

Abstract

backgroundOsteoporosis (OP) is a disease in which weak bones increase the risk of fracture. It has been reported that the occurrence of ferroptosis accelerated the progression of OP. However, the underlying mechanism of ferroptosis in OP remains unclear.

methodsClinical samples from OP patients were collected and ovariectomized (OVX)-induced mouse models with GPX4 knockout was established. The expression of genes and proteins was determined by RT-qPCR, western blot, IHC and IF. Bone mineral density (BMD) of the lumbar vertebrae was evaluated using DXA. Pearson correlation analysis was used to analyze the relationship between GPX4 expression and BMD. The femoral morphology was detected by HE staining. Images and relevant parameters of the femur were acquired using micro-CT. Ultrastructural changes in mitochondria were observed using TEM. MDA and GSH levels in mice and cells were examined using commercial kits. Lipid peroxidation was detected using Bodipy-C11 fluorescent probe. ALP activity was measured using ALP staining and calcified nodules were examined using ARS staining. The interaction between YAP1 and GPX4 promoter was validated using ChIP and dual-luciferase reporter gene assay.

resultsGPX4 expression was downregulated in clinical samples of OP and positively correlated with BMD. GPX4 knockout exacerbated bone loss and promoted ferroptosis in OVX-induced mice. Besides, GPX4 overexpression inhibited ferroptosis and enhanced osteogenic potential of osteoblasts. Moreover, YAP1 positively regulated GPX4 expression in osteoblasts through activating transcriptional activity of GPX4 promoter and YAP1 overexpression suppressed ferroptosis and enhanced osteogenic potential of osteoblasts via enhancing GPX4 expression.

conclusionGPX4 was positively regulated by YAP1, which in turn inhibited ferroptosis and enhanced osteogenic potential of osteoblasts, thereby alleviating OA progression.

Indexed as

Adaptor Proteins, Signal TransducingCell Cycle ProteinsFerroptosisOsteoblastsOsteoporosisPhospholipid Hydroperoxide Glutathione PeroxidaseYAP-Signaling ProteinsAnimalsBone DensityDisease Models, AnimalFemaleHumansMiceMice, KnockoutSignal TransductionAdaptor Proteins, Signal TransducingCell Cycle Proteinsglutathione peroxidase 4, mousePhospholipid Hydroperoxide Glutathione PeroxidaseYAP1 protein, humanYap1 protein, mouseYAP-Signaling ProteinsFerroptosisGPX4OsteoblastsOsteoporosisYAP1

Identifiers

PMID41120907
PMCPMC12539158

What Socratic 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 Socratic graph.