Evidence map›Paper›PMID 36284303›Full record

ArticleCell communication and signaling : CCS2022

Metformin alleviates bone loss in ovariectomized mice through inhibition of autophagy of osteoclast precursors mediated by E2F1.

Xudong Xie, Liangcong Hu, Bobin Mi, Hang Xue, Yiqiang Hu, Adriana C Panayi, Yori Endo, Lang Chen, Chenchen Yan, Ze Lin and 3 more

Open access · goldAbstract readVideo-Audio Media
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell communication and signaling : CCS, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed, 2 pooled it
2.4field-weighted citation impact, top 10% of its field
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

20 citing papers in PubMed, 2 syntheses or guidelines pooled it, 30 citations in OpenAlex.

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  9. Metformin and bone metabolism: unraveling their direct and indirect effects.Therapeutic advances in endocrinology and metabolism · 2025
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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

13 authors at 5 institutions in 2 countries.

Xudong Xie *Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
Liangcong Hu *Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
Bobin Mi *Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
Hang XueDepartment of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
Yiqiang HuDepartment of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
Adriana C PanayiDivision of Plastic Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 02215, USA.
Yori EndoDivision of Plastic Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 02215, USA.
Lang ChenDepartment of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
Chenchen YanDepartment of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
Ze LinDepartment of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
Hui LiDepartment of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China. lihuiunion@163.com.
Wu ZhouDepartment of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China. 2016XH0120@hust.edu.cn.
Guohui LiuDepartment of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China. liuguohui@hust.edu.cn.
Huazhong University of Science and Technology · CNHubei Zhongshan Hospital · CNUnion Hospital · CNBrigham and Women's Hospital · USWuhan University · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundPostmenopausal bone loss, mainly caused by excessive bone resorption mediated by osteoclasts, has become a global public health burden. Metformin, a hypoglycemic drug, has been reported to have beneficial effects on maintaining bone health. However, the role and underlying mechanism of metformin in ovariectomized (OVX)-induced bone loss is still vague.

resultsIn this study, we demonstrated for the first time that metformin administration alleviated bone loss in postmenopausal women and ovariectomized mice, based on reduced bone resorption markers, increased bone mineral density (BMD) and improvement of bone microstructure. Then, osteoclast precursors administered metformin in vitro and in vivo were collected to examine the differentiation potential and autophagical level. The mechanism was investigated by infection with lentivirus-mediated BNIP3 or E2F1 overexpression. We observed a dramatical inhibition of autophagosome synthesis and osteoclast formation and activity. Treatment with RAPA, an autophagy activator, abrogated the metformin-mediated autophagy downregulation and inhibition of osteoclastogenesis. Additionally, overexpression of E2F1 demonstrated that reduction of OVX-upregulated autophagy mediated by metformin was E2F1 dependent. Mechanistically, metformin-mediated downregulation of E2F1 in ovariectomized mice could downregulate BECN1 and BNIP3 levels, which subsequently perturbed the binding of BECN1 to BCL2. Furthermore, the disconnect between BECN1 and BCL2 was shown by BNIP3 overexpression.

conclusionIn summary, we demonstrated the effect and underlying mechanism of metformin on OVX-induced bone loss, which could be, at least in part, ascribed to its role in downregulating autophagy during osteoclastogenesis via E2F1-dependent BECN1 and BCL2 downregulation, suggesting that metformin or E2F1 inhibitor is a potential agent against postmenopausal bone loss. Video abstract.

Indexed as

Bone ResorptionMetforminOsteoporosis, PostmenopausalAnimalsAutophagyCell DifferentiationE2F1 Transcription FactorFemaleHumansHypoglycemic AgentsMiceOsteoclastsProto-Oncogene Proteins c-bcl-2RANK LigandE2F1 protein, humanE2F1 Transcription FactorHypoglycemic AgentsMetforminProto-Oncogene Proteins c-bcl-2RANK LigandAutophagyBECN1BNIP3Bone lossE2F1MetforminOsteoclast precursors

Identifiers

PMID36284303
PMCPMC9594975
OpenAlexW4307199210

What OpenQuestion 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 OpenQuestion graph.