Evidence map›Paper›PMID 36328754›Full record

ArticleJournal of advanced research2022

Mechanical overloading induces GPX4-regulated chondrocyte ferroptosis in osteoarthritis via Piezo1 channel facilitated calcium influx.

Shaoyi Wang, Weiwei Li, Pengfei Zhang, Zihao Wang, Xiaoyuan Ma, Chuanju Liu, Krasimir Vasilev, Lei Zhang, Xiaocong Zhou, Liang Liu and 6 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of advanced research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 179 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
179citing papers in PubMed, 3 pooled it
20.1field-weighted citation impact, top 1% 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

179 citing papers in PubMed, 3 syntheses or guidelines pooled it, 238 citations in OpenAlex.

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119 more citing papers are in PubMed but not listed here.

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

16 authors at 6 institutions in 3 countries.

Shaoyi WangDepartment of Orthopaedic Surgery, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250012, PR China; Qilu Hospital of Shandong University Spine and Spinal Cord Disease Research Center-ICMRS Collaborating Center for Orthopaedic translational Research, Shandong University, Jinan, Shandong 250012, PR China; Institute of Stomatology, Shandong University, Jinan, Shandong, 250012, PR China; NHC Key Laboratory of Otorhinolaryngology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250012, PR China.
Weiwei LiDepartment of Pathology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250012, PR China.
Pengfei ZhangDepartment of Orthopaedic Surgery, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250012, PR China; Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250012, PR China.
Zihao WangQilu Hospital of Shandong University Spine and Spinal Cord Disease Research Center-ICMRS Collaborating Center for Orthopaedic translational Research, Shandong University, Jinan, Shandong 250012, PR China; Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250012, PR China.
Xiaoyuan MaDepartment of Orthopaedic Surgery, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250012, PR China.
Chuanju LiuDepartment of Orthopaedic Surgery, New York University School of Medicine, New York University Medical Center, New York City, NY, USA.
Krasimir VasilevFuture Industries Institute, University of South Australia, Mawson Lakes Campus, Mawson Lakes 5095, Australia; School of Engineering, University of South Australia, Mawson Lakes Campus, Mawson Lakes 5095, Australia.
Lei ZhangDepartment of Orthopaedic Surgery, The First Affiliated Hospital of Shandong First Medical University, Jinan, Shandong 250012, PR China.
Xiaocong ZhouHealth Management Centre. The First Affiliated Hospital of Shandong First Medical University, Jinan, Shandong 250012, PR China.
Liang LiuExperimental Therapeutics Laboratory, University of South Australia Cancer Research Institute, Adelaide SA 5000, Australia.
John HayballExperimental Therapeutics Laboratory, University of South Australia Cancer Research Institute, Adelaide SA 5000, Australia; Robinson Research Institute and Adelaide Medical School, University of Adelaide, Adelaide SA 5005, Australia.
Shuli DongKey Laboratory of Colloid and Interface Chemistry (Shandong University), Ministry of Education, Jinan 250100, PR China.
Yuhua LiDepartment of Orthopaedic Surgery, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250012, PR China.
Yuan GaoDepartment of Orthopaedic Surgery, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250012, PR China.
Lei ChengDepartment of Orthopaedic Surgery, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250012, PR China; Qilu Hospital of Shandong University Spine and Spinal Cord Disease Research Center-ICMRS Collaborating Center for Orthopaedic translational Research, Shandong University, Jinan, Shandong 250012, PR China. Electronic address: chenglei@email.sdu.edu.cn.
Yunpeng ZhaoDepartment of Orthopaedic Surgery, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250012, PR China. Electronic address: lwwzyp@email.sdu.edu.cn.
Shandong University · CNCentre for Cancer Biology · AUQilu Hospital of Shandong University · CNShandong First Medical University · CNColumbia University Irving Medical Center · USUniversity of South Australia · AU

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

introductionsExcessive mechanical stress is closely associated with cell death in various conditions. Exposure of chondrocytes to excessive mechanical loading leads to a catabolic response as well as exaggerated cell death. Ferroptosis is a recently identified form of cell death during cell aging and degeneration. However, it's potential association with mechanical stress remains to be illustrated.

objectivesTo identify whether excessive mechanical stress can cause ferroptosis. To explore the role of mechanical overloading in chondrocyte ferroptosis.

methodsChondrocytes were collected from loading and unloading zones of cartilage in patients with osteoarthritis (OA), and the ferroptosis phenotype was analyzed through transmission electron microscope and microarray. Moreover, the relationship between ferroptosis and OA was analyzed by GPX4-conditional knockout (Col2a1-CreERT: GPX4

resultsHuman cartilage and mouse chondrocyte experiments revealed that mechanical overloading can induce GPX4-associated ferroptosis. Conditional knockout of GPX4 in cartilage aggravated experimental OA process, while additional treatment with ferroptosis suppressor protein (FSP-1) and coenzyme Q10 (CoQ10) abated OA development in GPX4-CKO mice. In mouse OA model and chondrocyte experiments, inhibition of Piezo1 channel activity increased GPX4 expression, attenuated ferroptosis phenotype and reduced the severity of osteoarthritis. Additionally, high strain mechanical stress induced ferroptosis damage in chondrocyte was largely abolished by blocking calcium influx through calcium-free medium.

conclusionsOur findings show that mechanical overloading induces ferroptosis through Piezo1 activation and subsequent calcium influx in chondrocytes, which might provide a potential target for OA treatment.

Indexed as

Cartilage, ArticularFerroptosisOsteoarthritisAnimalsChondrocytesDisease Models, AnimalHumansIon ChannelsMicePhospholipid Hydroperoxide Glutathione PeroxidaseStress, Mechanicalglutathione peroxidase 4, mouseIon ChannelsPhospholipid Hydroperoxide Glutathione PeroxidasePIEZO1 protein, humanPiezo1 protein, mouseChondrocytesFerroptosisMechanical stressOsteoarthritisPiezo1

Identifiers

PMID36328754
PMCPMC9637484
OpenAlexW4206521993

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.