Evidence map›Paper›PMID 33123307›Full record

ArticleOxidative medicine and cellular longevity2020

ROS-Mediated Necroptosis Is Involved in Iron Overload-Induced Osteoblastic Cell Death.

Qing Tian, Bo Qin, Yufan Gu, Lijun Zhou, Songfeng Chen, Song Zhang, Shuhao Zhang, Qicai Han, Yong Liu, Xuejian Wu

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

Article in Oxidative medicine and cellular longevity, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
69citing papers in PubMed, 2 pooled it
4.9field-weighted citation impact, top 4% 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

69 citing papers in PubMed, 2 syntheses or guidelines pooled it, 114 citations in OpenAlex.

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9 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

10 authors at 2 institutions in 1 country.

Qing TianDepartment of Orthopaedics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China.
Bo QinDepartment of Translational Medical Center, First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China.
Yufan GuDepartment of Orthopaedics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China.
Lijun ZhouDepartment of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
Songfeng ChenDepartment of Orthopaedics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China.
Song ZhangDepartment of Orthopaedics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China.
Shuhao ZhangDepartment of Orthopaedics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China.
Qicai HanDepartment of Orthopaedics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China.ORCID https://orcid.org/0000-0002-9254-6478
Yong LiuDepartment of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
Xuejian WuDepartment of Orthopaedics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China.
First Affiliated Hospital of Zhengzhou University · CNUnion Hospital · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Excess iron has been reported to lead to osteoblastic cell damage, which is a crucial pathogenesis of iron overload-related osteoporosis. However, the cytotoxic mechanisms have not been fully documented. In the present study, we focused on whether necroptosis contributes to iron overload-induced osteoblastic cell death and related underlying mechanisms. Here, we showed that the cytotoxicity of iron overload in osteoblastic cells was mainly due to necrosis, as evidenced by the Hoechst 33258/PI staining, Annexin-V/PI staining, and transmission electronic microscopy. Furthermore, we revealed that iron overload-induced osteoblastic necrosis might be mediated via the RIPK1/RIPK3/MLKL necroptotic pathway. In addition, we also found that iron overload was able to trigger mitochondrial permeability transition pore (mPTP) opening, which is a critical downstream event in the execution of necroptosis. The key finding of our experiment was that iron overload-induced necroptotic cell death might depend on reactive oxygen species (ROS) generation, as N-acetylcysteine effectively rescued mPTP opening and necroptotic cell death. ROS induced by iron overload promote necroptosis via a positive feedback mechanism, as on the one hand N-acetylcysteine attenuates the upregulation of RIPK1 and RIPK3 and phosphorylation of RIPK1, RIPK3, and MLKL and on the other hand Nec-1, siRIPK1, or siRIPK3 reduced ROS generation. In summary, iron overload induced necroptosis of osteoblastic cells in vitro, which is mediated, at least in part, through the RIPK1/RIPK3/MLKL pathway. We also highlight the critical role of ROS in the regulation of iron overload-induced necroptosis in osteoblastic cells.

Indexed as

AcetylcysteineAnimalsCell DeathCell LineFerric CompoundsImidazolesIndolesMembrane Potential, MitochondrialMiceMitochondrial Permeability Transition PoreNecroptosisOsteoblastsPhosphorylationProtein KinasesQuaternary Ammonium CompoundsReactive Oxygen SpeciesAcetylcysteineferric ammonium citrateFerric CompoundsImidazolesIndolesMitochondrial Permeability Transition PoreMLKL protein, mousenecrostatin-1Protein KinasesQuaternary Ammonium CompoundsReactive Oxygen SpeciesReceptor-Interacting Protein Serine-Threonine KinasesRipk1 protein, mouseRipk3 protein, mouseRNA, Small Interfering

Identifiers

PMID33123307
PMCPMC7586162
OpenAlexW3093301274

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.