Evidence map›Paper›PMID 40436926›Full record

ArticleScientific reports2025

Estradiol and vitamin D exert a synergistic effect on preventing osteoporosis via the miR-351-5p/IRS1 axis and mTOR/NFκB signaling pathway.

Xiaoyan Dai, Changcun Liu, Wenkai Bi, Guiwen Zheng, Kuan Lv, Zhiming Xia

Abstract read
In one paragraph

Article in Scientific reports, 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. Article
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

6 authors.

Xiaoyan DaiDepartment of Otolaryngology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China.
Changcun LiuDepartment of Nuclear Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, P.R. China.
Wenkai BiDepartment of Nuclear Medicine, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China.
Guiwen ZhengDepartment of Nuclear Medicine, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China.
Kuan LvDepartment of Nuclear Medicine, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China.
Zhiming XiaDepartment of Nuclear Medicine, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China. zm.xia@126.com.

Funding

Shandong Provincial Natural Science Foundation BS2014YY044、ZR2022MH121
6 · The paper itself

Abstract

This study aimed to investigate the antiosteoporotic effects and regulatory mechanisms of estradiol (E2) and vitamin D. MC3T3-E1 cells were treated with E2, vitamin D, or their combination, followed by a systematic assessment of cell proliferation and osteogenic differentiation capacity across the treatment groups. Subsequently, miRNA sequencing was performed to analyze differentially expressed miRNAs between the control and E2&vitamin D groups. The target relationship between miR-351-5p and IRS1 was validated, and the effects of the miR-351-5p/IRS1 axis on osteogenesis and mTOR/NFκB signaling pathway were determined after combination treatment. Additionally, an ovariectomized (OVX) osteoporosis mouse model was established to ‌systematically examine‌ the effects of E2, vitamin D, and their combination on osteoporosis and mTOR/NFκB signaling pathway. E2 and vitamin D synergistically promoted MC3T3-E1 cell proliferation and osteogenic differentiation. miR-351-5p was identified through miRNA sequencing analysis. miR-351-5p was downregulated in MC3T3-E1 cells after E2 and vitamin D combination treatment, and its overexpression partially reversed the effect of the combination treatment on osteogenesis. IRS1 was a target of miR-351-5p. When overexpressed, IRS1 partially mitigated the impact of miR-351-5p overexpression on osteogenesis and mTOR/NFκB signaling pathway under the combination treatment. Furthermore, in vivo experiments demonstrated that E2 and vitamin D could synergistically prevent osteoporosis in OVX mice by inhibiting the mTOR/NFκB signaling pathway. In conclusion, E2 and vitamin D exhibited a synergistic effect in preventing osteoporosis through the miR-351-5p/IRS1 axis and mTOR/NFκB signaling pathway. E2 and vitamin D combination treatment could be a potential anti-osteoporotic strategy for osteoporosis treatment.

Indexed as

EstradiolInsulin Receptor Substrate ProteinsMicroRNAsOsteoporosisSignal TransductionTOR Serine-Threonine KinasesVitamin DAnimalsCell DifferentiationCell LineCell ProliferationDisease Models, AnimalDrug SynergismFemaleMiceNF-kappa BEstradiolInsulin Receptor Substrate ProteinsIrs1 protein, mouseMicroRNAsmTOR protein, mouseNF-kappa BTOR Serine-Threonine KinasesVitamin DEstradiolIRS1miR-351-5pmTOR/NFκB signaling pathwayOsteoporosisVitamin D

Identifiers

PMID40436926
PMCPMC12119810

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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.