Evidence map›Paper›PMID 39647633›Full record

ArticleJournal of advanced research2025

Asperosaponin VI inhibition of DNMT alleviates GPX4 suppression-mediated osteoblast ferroptosis and diabetic osteoporosis.

Fanhao Wei, Binjia Ruan, Jian Dong, Bin Yang, Guofu Zhang, Wai Kwok Kelvin Yeung, Hongwei Wang, Wangsen Cao, Yongxiang Wang

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PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of advanced research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
33citing 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

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

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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

9 authors.

Fanhao WeiDepartment of Graduate School, Dalian Medical University, No.9 of West Section of Lushun South Road, Dalian 116044, China; The Yangzhou School of Clinical Medicine of Dalian Medical University, 98 West Nantong Road, Yangzhou 225001, China.
Binjia RuanNorthern Jiangsu People's Hospital, Clinical Teaching Hospital of Medical School, Nanjing University, 98 West Nantong Road, Yangzhou 225001, China.
Jian DongDepartment of Thoracic Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu 210093, China.
Bin YangDepartment of Orthopaedics, Northern Jiangsu People's Hospital Affiliated to Yangzhou University, 98 West Nantong Road, Yangzhou 225001, China.
Guofu ZhangDepartment of Orthopaedics, Northern Jiangsu People's Hospital Affiliated to Yangzhou University, 98 West Nantong Road, Yangzhou 225001, China.
Wai Kwok Kelvin YeungDepartment of Orthopaedics and Traumatology, School of Clinical Medicine, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong, China.
Hongwei WangNanjing University Medical School, Jiangsu Key Lab of Molecular Medicine, 22 Hankou Road, Nanjing 210093, China. Electronic address: hwang@nju.edu.cn.
Wangsen CaoDepartment of Orthopaedics, Northern Jiangsu People's Hospital Affiliated to Yangzhou University, 98 West Nantong Road, Yangzhou 225001, China; Nanjing University Medical School, Jiangsu Key Lab of Molecular Medicine, 22 Hankou Road, Nanjing 210093, China; Yancheng First People's Hospital, Affiliated Hospital of Nanjing University Medical School, South People's Road, Yancheng 224006, China.. Electronic address: wangsencao@nju.edu.cn.
Yongxiang WangDepartment of Orthopaedics, Northern Jiangsu People's Hospital Affiliated to Yangzhou University, 98 West Nantong Road, Yangzhou 225001, China; Department of Orthopaedics, Northern Jiangsu People's Hospital, 98 West Nantong Road, Yangzhou 225001, China; The Yangzhou School of Clinical Medicine of Dalian Medical University, 98 West Nantong Road, Yangzhou 225001, China; Northern Jiangsu People's Hospital, Clinical Teaching Hospital of Medical School, Nanjing University, 98 West Nantong Road, Yangzhou 225001, China. Electronic address: wyx918spine@yzu.edu.cn.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

introductionDiabetic osteoporosis (DOP) is an insidious complication of diabetes with limited therapeutic options. DOP is pathologically associated with various types of regulated cell death, but the precise role of ferroptosis in the process remains poorly understood. Asperosaponin VI (AVI), known for its clinical efficacy in treating bone fractures and osteoporosis, may exert its osteoprotective effects through mechanisms involving ferroptosis, however this has not been established.

objectivesThis study aimed to investigate the role of AVI in modulating ferroptosis in a mouse model of DOP and to explore the underlying mechanisms.

methodsWe assessed OP alterations in femurs of DOP-conditioned mice and primary bone cells. We generated a strain of osteoblast-specific Gpx4-deficient mice. A combination of micro-CT, immunohistochemistry, immunofluorescence, methylation-specific PCR (MSP), bisulfite sequencing PCR (BSP), western blotting (WB), and AVI pull-down assays were employed to elucidate the mechanism and therapeutic target of AVI in DOP.

resultsOur findings revealed that femurs from DOP-conditioned mice exhibited significant ferroptosis and suppression of the core anti-ferroptosis factor GPX4, mainly due to hypermethylation of the Gpx4 promoter mediated by DNA methyltransferases DNMT1and DNMT3a. Notably, treatment with AVI effectively reversed the hypermethylation, restored GPX4 expression, and reduced ferroptotic pathologies associated with DOP by inhibiting DNMT1/3a. In primarily-cultured osteoblasts and osteoclasts, AVI alleviated GPX4 suppression and reduced ferroptosis in DOP-conditioned osteoblasts through a mechanism dependent on DNMT inhibition and GPX4 restoration. Importantly, the anti-ferroptotic and osteoprotective effects of AVI were abolished in osteoblastic Gpx4 haplo-deficient mice (Gpx4

conclusionsOur study identifies a pivotal epigenetic ferroptotic pathway that contributes significantly to DOP and uncovers a crucial pharmacological property of AVI that is potentially effective in treating patients with DOP and related osteoporotic disorders.

Indexed as

Diabetes ComplicationsDNA (Cytosine-5-)-Methyltransferase 1FerroptosisOsteoblastsOsteoporosisPhospholipid Hydroperoxide Glutathione PeroxidaseSaponinsAnimalsDiabetes Mellitus, ExperimentalDisease Models, AnimalDNA MethylationMaleMiceMice, Inbred C57BLMice, Knockoutakebia saponin DDNA (Cytosine-5-)-Methyltransferase 1glutathione peroxidase 4, mousePhospholipid Hydroperoxide Glutathione PeroxidaseSaponinsAsperosaponin VIDiabetic OsteoporosisDNA methylationFerroptosisGPX4

Identifiers

PMID39647633
PMCPMC12536592

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Registered trials

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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.