Evidence map›Paper›PMID 40159493›Full record

ArticleMolecular medicine (Cambridge, Mass.)2025

Metformin ameliorates osteoporosis by enhancing bone angiogenesis via the YAP1/TAZ-HIF1α axis.

Hao Yin, Zhe Ruan, Teng-Fei Wan, Zhi-Rou Lin, Chun-Yuan Chen, Zhen-Xing Wang, Jia Cao, Yi-Yi Wang, Ling Jin, Yi-Wei Liu and 12 more

Abstract read
PubMed Full text at PMC Publisher
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 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing 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

6 citing papers in PubMed.

  1. Review
  2. Article
  3. Article
  4. Metformin Promotes Osteogenic Differentiation by Inducing AutophagyEndocrine, metabolic & immune disorders drug targets · 2026
    Article
  5. Article
  6. 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

22 authors.

Hao Yin *Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China.
Zhe Ruan *Department of Orthopedics, The First Hospital of Changsha, Changsha, 410008, Hunan, China.
Teng-Fei WanDepartment of Orthopedics, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China.
Zhi-Rou LinThe First Affiliated Hospital, Department of Metabolism and Endocrinology, Hengyang Medical School, University of South China, Hengyang, 421001, Hunan, China.
Chun-Yuan ChenDepartment of Orthopedics, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China.
Zhen-Xing WangDepartment of Orthopedics, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China.
Jia CaoDepartment of Orthopedics, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China.
Yi-Yi WangDepartment of Orthopedics, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China.
Ling JinDepartment of Orthopedics, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China.
Yi-Wei LiuDepartment of Orthopedics, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China.
Guo-Qiang ZhuDepartment of Orthopedics, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China.
Jiang-Shan GongDepartment of Orthopedics, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China.
Jing-Tao ZouDepartment of Orthopedics, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China.
Yi LuoDepartment of Orthopedics, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China.
Yin HuThe First Affiliated Hospital, Department of Metabolism and Endocrinology, Hengyang Medical School, University of South China, Hengyang, 421001, Hunan, China.
Zhao-Hui LiDepartment of Orthopedics, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China.
Hao LuoDepartment of Orthopedics, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China.
Yu-Qi LiuDepartment of Orthopedics, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China.
Cheng LongDepartment of Orthopedics, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China.
Shu-Shan ZhaoDepartment of Orthopedics, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China. shushanzhao@csu.edu.cn.
Yong ZhuDepartment of Orthopedics, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China. doczhu2003@aliyun.com.
Hui XieDepartment of Orthopedics, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China. huixie@csu.edu.cn.

Funding

Foundation for Innovative Research Groups of the National Natural Science Foundation of China 81874006Foundation for Innovative Research Groups of the National Natural Science Foundation of China 82072504Hunan Province Natural Science Foundation of China 2021JJ40492National Natural Science Foundation of China 81871822National Natural Science Foundation of China 81902222National Natural Science Foundation of China 82000845National Natural Science Foundation of China 82172399National Outstanding Youth Science Fund Project of National Natural Science Foundation of China 82125023
6 · The paper itself

Abstract

backgroundOsteoporosis, resulting from an imbalance between osteoclast-mediated bone resorption and osteoblast-mediated bone formation, affects millions globally. Recent studies have identified type H vessels (CD31

methodsOsteoporotic mice were administered metformin, and bone mass and strength were measured. In vivo and in vitro angiogenesis assays were performed under hypoxic conditions. Expression levels of YAP1/TAZ and HIF1α were assessed in femoral metaphysis and hypoxia-cultured human microvascular endothelial cells (HMECs). Small interfering RNA was used to interfere with HIF1α or YAP1/TAZ expression in hypoxia-cultured HMECs. Additionally, we employed AAV-mediated overexpression of YAP1/TAZ in vivo to determine whether elevated YAP1/TAZ levels alter metformin's effects on bone mass and angiogenesis.

resultsMetformin significantly enhanced bone mass and strength in osteoporotic mice. It also promoted angiogenesis under hypoxia conditions both in vivo and in vitro. Metformin reduced YAP1/TAZ expression while increasing HIF1α expression in both the femoral metaphysis of osteoporotic mice and hypoxia-cultured HMECs. Interference with HIF1α or YAP1/TAZ confirmed that metformin enhances HIF1α and its target genes primarily by inhibiting YAP1/TAZ. Furthermore, overexpression of YAP1/TAZ partially reversed the bone-protective effect of metformin, leading to reduced HIF1α levels and diminished type H vessel formation.

conclusionOur findings suggest that metformin holds promise as a therapeutic agent for osteoporosis by enhancing type H vessel formation through the inhibition of the YAP1/TAZ-HIF1α axis.

Indexed as

Adaptor Proteins, Signal TransducingBone and BonesHypoxia-Inducible Factor 1, alpha SubunitMetforminNeovascularization, PhysiologicOsteoporosisTranscription FactorsAcyltransferasesAngiogenesisAnimalsDisease Models, AnimalFemaleHumansMiceSignal TransductionTrans-ActivatorsAcyltransferasesAdaptor Proteins, Signal TransducingHif1a protein, mouseHypoxia-Inducible Factor 1, alpha SubunitMetforminTrans-ActivatorsTranscriptional Coactivator with PDZ-Binding Motif ProteinsTranscription FactorsWwtr1 protein, mouseYap1 protein, mouseYAP-Signaling ProteinsAngiogenesisHIF1αMetforminOsteoporosisType H vesselYAP1/TAZ

Identifiers

PMID40159493
PMCPMC11955141

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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.