Evidence map›Paper›PMID 38493104›Full record

ArticleArthritis research & therapy2024

TfR1 mediated iron metabolism dysfunction as a potential therapeutic target for osteoarthritis.

Wenchao Wang, Zhenkai Ma, Xuemin Feng, Jiabin Ren, Shengyao Sun, Yuandong Shao, Weimin Zhang, Xiaoxia Yang, Jiaming Zhang, Xingzhi Jing

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

Article in Arthritis research & therapy, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed
5.7field-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

19 citing papers in PubMed, 20 citations in OpenAlex.

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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

10 authors at 5 institutions in 1 country.

Wenchao WangDepartment of Spine Surgery, Shandong Provincial Hospital affiliated to Shandong First Medical University, Jinan, 250000, Shandong, China.
Zhenkai MaDepartment of Neurosurgery, Binzhou People's Hospital, Binzhou, 256600, China.
Xuemin FengDepartment of Endocrinology, Binzhou People's Hospital, Binzhou, 256600, China.
Jiabin RenDepartment of Spine Surgery, Binzhou Medical University Hospital, Binzhou, 256600, China.
Shengyao SunShandong First Medical University & Shandong Academy of Medical Sciences, No.6699 Qingdao Road, Jinan, 250117, China.
Yuandong ShaoDepartment of Spine Surgery, Binzhou People's Hospital, Binzhou, 256600, China.
Weimin ZhangDepartment of Spine Surgery, Shandong Provincial Hospital affiliated to Shandong First Medical University, Jinan, 250000, Shandong, China.
Xiaoxia YangDepartment of Spine Surgery, Shandong Provincial Hospital affiliated to Shandong First Medical University, Jinan, 250000, Shandong, China.
Jiaming ZhangClinical Innovation & Research Center (CIRC), Shenzhen Hospital, Southern Medical University, Shenzhen, 518100, China. jiaming_zhangtjmc@icloud.com.
Xingzhi JingDepartment of Spine Surgery, Shandong Provincial Hospital affiliated to Shandong First Medical University, Jinan, 250000, Shandong, China. jingxingzhi@sdfmu.edu.cn.
Binzhou People's Hospital · CNShandong First Medical University · CNShandong Provincial Hospital · CNBinzhou Medical University · CNSouthern Medical University Shenzhen Hospital · CN

Funding

National Natural Science Foundation of China 82002325Natural Science Foundation of Shandong Province ZR2022LZY001
6 · The paper itself

Abstract

objectiveTransferrin receptor-1 (TfR1) plays important roles in controlling cellular iron levels, but its role in OA pathology is unknown. Herein we aim to investigate the role of TfR1 in OA progression and its underlying mechanisms.

methodsTfR1 expression in cartilage during OA development were examined both in vivo and in vitro. Then IL-1β was used to induce chondrocytes degeneration in vitro and TfR1 siRNA was used for observing the effect of TfR1 in modulating iron homeostasis, mitochondrial function and degrading enzymes expression. Also the inhibitor of TfR1 was exploited to analyze the protective effect of TfR1 inhibition in vivo.

resultsTfR1 is elevated in OA cartilage and contributes to OA inflammation condition. Excess iron not only results in oxidative stress damage and sensitizes chondrocytes to ferroptosis, but also triggers c-GAS/STING-mediated inflammation by promoting mitochondrial destruction and the release of mtDNA. Silencing TfR1 using TfR1 siRNA not only reduced iron content in chondrocytes and inhibited oxidative stress, but also facilitated the mitophagy process and suppressed mtDNA/cGAS/STING-mediated inflammation. Importantly, we also found that Ferstatin II, a novel and selective TfR1 inhibitor, could substantially suppress TfR1 activity both in vivo and in vitro and ameliorated cartilage degeneration.

conclusionOur work demonstrates that TfR1 mediated iron influx plays important roles in chondrocytes degeneration and OA pathogenesis, suggesting that maintaining iron homeostasis through the targeting of TfR1 may represent a novel therapeutic strategy for the treatment of OA.

Indexed as

OsteoarthritisCartilageChondrocytesDNA, MitochondrialHumansInflammationRNA, Small InterferingDNA, MitochondrialRNA, Small InterferingcGAS/STING pathwayIron metabolismMitophagymtDNATransferrin receptor-1 (TfR1)

Identifiers

PMID38493104
PMCPMC10943767
OpenAlexW4392883247

What OpenQuestion holds

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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.