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ArticleMolecular biology reports2026

m6A RNA modifications in neurosystem genes as early markers for osteoporosis with iron accumulation.

Baoshan Liu, Yike Wang, Miao Zheng, Kai Huang, Jianzhong Qin, Qiaocheng Zhai, Youjia Xu

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Article in Molecular biology reports, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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7 authors.

Baoshan Liu *Department of Orthopaedics, The Second Affiliated, Hospital of Soochow University, NO.1055 SanXiang Road, Suzhou, 215004, Jiangsu Province, China.
Yike Wang *Department of Orthopaedics, The Second Affiliated, Hospital of Soochow University, NO.1055 SanXiang Road, Suzhou, 215004, Jiangsu Province, China.
Miao ZhengDepartment of Orthopaedics, The Second Affiliated, Hospital of Soochow University, NO.1055 SanXiang Road, Suzhou, 215004, Jiangsu Province, China.
Kai HuangOrthopaedic Institute, Wuxi 9th People's Hospital Affiliated to Soochow University, Wuxi, Jiangsu, China.
Jianzhong QinDepartment of Orthopaedics, The Second Affiliated, Hospital of Soochow University, NO.1055 SanXiang Road, Suzhou, 215004, Jiangsu Province, China.
Qiaocheng ZhaiDepartment of Orthopaedics, The Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou People's Hospital, Zhejiang, China. zhaiqiaocheng@wmu.edu.cn.
Youjia XuDepartment of Orthopaedics, The Second Affiliated, Hospital of Soochow University, NO.1055 SanXiang Road, Suzhou, 215004, Jiangsu Province, China. xuyoujia@suda.edu.cn.

Funding

Jiangsu Provincial Medical Key Laboratory Cultivation Unit JSDW202254Suzhou Science and Education Youth Project KJXW2023015The Second Affiliated Hospital of Soochow University, Key Talent Project for Medical Application of Nuclear Technology XKTJ-HRC2021005The Second Affiliated Hospital of Soochow University Scientific Research Pre-Research Fund Project SDFEYBS2202231370
6 · The paper itself

Abstract

backgroundPostmenopausal osteoporosis is a prevalent bone disorder, and recent evidence suggests that iron accumulation, particularly within the nervous system, may exacerbate bone loss through epigenetic mechanisms. This study aims to investigate the role of m6A RNA methylation in the regulation of bone metabolism under conditions of iron overload in a postmenopausal osteoporotic model.

methodsFifteen female C57BL/6J mice were divided into three groups: sham-operated, ovariectomized (ovx), and ovariectomized with iron–dextran intervention (ovx+iron). Ovariectomy was performed at 8 weeks of age, followed by 8 weeks of iron–dextran administration to establish the model. Bone RNA samples were subjected to methylated RNA immunoprecipitation sequencing (MeRIP-seq) to profile m6A modifications. Bone morphology and iron status were evaluated using microCT scanning, immunohistochemistry, and Prussian blue staining.

resultsThe ovx+iron group exhibited a higher number of m6A peaks (27,167) compared to the ovx group (21,441), with significant differences in methylation patterns. Upregulated differentially methylated genes (DMGs) were enriched in pathways related to nervous system development and skeletal morphogenesis, while downregulated DMGs were associated with epithelial morphogenesis and Wnt signaling. Integrative analysis identified 150 genes with concurrent alterations in mRNA expression and m6A modification, highlighting neural regulatory influences on bone mass under iron accumulation. Notably, Lep, a critical neural regulator, showed reduced expression and decreased m6A methylation in the ovx+iron group, which was further confirmed at the protein level by immunohistochemistry.

conclusionIron accumulation induces significant changes in m6A methylation, which may disrupt bone metabolism by modulating neural factors such as Leptin. These findings suggest that Leptin could serve as a potential early diagnostic biomarker for postmenopausal osteoporosis complicated by iron overload.

Indexed as

IronIron OverloadOsteoporosisOsteoporosis, PostmenopausalAnimalsBiomarkersDisease Models, AnimalEpitranscriptomeFemaleMiceMice, Inbred C57BLOvariectomyRNA MethylationBiomarkersIronEpigeneticsIron accumulationLeptinm6A methylationPostmenopausal osteoporosis

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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.