Evidence map›Paper›PMID 35765024›Full record

ArticleJournal of orthopaedic surgery and research2022

Metformin alleviates osteoarthritis in mice by inhibiting chondrocyte ferroptosis and improving subchondral osteosclerosis and angiogenesis.

Jiangbo Yan, Gangning Feng, Long Ma, Zhirong Chen, Qunhua Jin

Open access · goldFull text read
In one paragraph

Article in Journal of orthopaedic surgery and research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
36citing papers in PubMed, 2 pooled it
5.8field-weighted citation impact, top 3% 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

36 citing papers in PubMed, 2 syntheses or guidelines pooled it, 63 citations in OpenAlex.

  1. Pooled it
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  13. Metformin and bone metabolism: unraveling their direct and indirect effects.Therapeutic advances in endocrinology and metabolism · 2025
    Review
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  16. Article
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  19. Ferroptosis in Arthritis: Driver of the Disease or Therapeutic Option?International journal of molecular sciences · 2024
    Review
  20. Review
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

5 authors at 1 institution in 1 country.

Jiangbo YanNingxia Medical University, The General Hospital of Ningxia Medical University, Yinchuan, Ningxia, China.
Gangning FengNingxia Medical University, The General Hospital of Ningxia Medical University, Yinchuan, Ningxia, China.
Long MaOrthopedics Ward 3, The General Hospital of Ningxia Medical University, Yinchuan, Ningxia, China.
Zhirong ChenNingxia Medical University, The General Hospital of Ningxia Medical University, Yinchuan, Ningxia, China. chenzhirong202204@163.com.
Qunhua JinNingxia Medical University, The General Hospital of Ningxia Medical University, Yinchuan, Ningxia, China. jinqunhua2020@163.com.
Ningxia Medical University · CN

Funding

National Natural Science Foundation of China 8216090355The Scientific Research Project from Ningxia Province 2020AAC03390The Scientific Research Project from Ningxia Province 2020AAC03392
6 · The paper itself

Abstract

backgroundOsteoarthritis (OA) is the most common musculoskeletal disease, and it has a complex pathology and unknown pathogenesis. Chondrocyte ferroptosis is closely associated with the development of OA. As a common drug administered for the treatment of type 2 diabetes, metformin (Met) is known to inhibit the development of ferroptosis. However, its therapeutic effect in OA remains unknown. The present study aimed to explore the effects of Met on cartilage and subchondral bone in a mouse OA model and to explore the potential underlying mechanisms.

methodsA mouse OA model was induced using destabilization of the medial meniscus (DMM) surgery, chondrocyte ferroptosis was induced using an intra-articular injection of Erastin, and Met (200 mg/kg/day) was intragastrically administered for 8 weeks after surgery. H&E and Safranin O‑fast green staining were used to evaluate cartilage degeneration, and μ‑computed tomography was used to evaluate changes in subchondral bone microarchitecture. Moreover, immunohistochemical staining was performed to detect mechanistic metalloproteinases 13, type II collagen, glutathione peroxidase 4, acyl-CoA synthetase long-chain family member 4, solute carrier family 7 member 11 and p53. Runt-associated transcription factor 2 and CD31 were detected using immunofluorescent staining.

resultsMet protected articular cartilage and reversed the abnormal expression of ferroptosis-related proteins in the chondrocytes of DMM mice. Moreover, intra-articular injection of Erastin induced ferroptosis in mouse chondrocytes, and Met eliminated the ferroptosis effects induced by Erastin and protected articular cartilage. In addition, the results of the present study demonstrated that Met alleviated the microstructural changes of subchondral osteosclerosis and reduced heterotypic angiogenesis in DMM mice.

conclusionMet alleviates the pathological changes of OA by inhibiting ferroptosis in OA chondrocytes, alleviating subchondral sclerosis and reducing abnormal angiogenesis in subchondral bone in advanced OA.

Indexed as

Diabetes Mellitus, Type 2FerroptosisMetforminOsteoarthritisOsteosclerosisAnimalsChondrocytesDisease Models, AnimalMiceNeovascularization, PathologicMetforminAngiogenesisChondrocytesFerroptosisMetforminOsteoarthritisSubchondral osteosclerosis

Identifiers

PMID35765024
PMCPMC9238069
OpenAlexW4283650657

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LicenceCC BY
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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.