Evidence map›Paper›PMID 40629421›Full record

ArticleJournal of orthopaedic surgery and research2025

VMP1 attenuates ferroptosis and mitochondrial dysfunction in nucleus pulposus cells through the PINK1/Parkin-mediated mitophagy pathway.

Yang Zhang, Yucheng Gao, Shuanggong Liu, Guowei Yang, Yijun Rong, Dongjin Wu, Zengxin Gao

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Article in Journal of orthopaedic surgery and research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

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0cells of the map it votes in
5citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

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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

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3 · Its place in the literature

Who cites it

5 citing papers in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

7 authors.

Yang Zhang *Department of Spinal Surgery, Zhongda Hospital, College of Medicine, Southeast University, NO.87 Ding Jia Qiao, Nanjing, Jiangsu, 210009, People's Republic of China.
Yucheng Gao *Department of Spinal Surgery, Zhongda Hospital, College of Medicine, Southeast University, NO.87 Ding Jia Qiao, Nanjing, Jiangsu, 210009, People's Republic of China.
Shuanggong LiuDepartment of Orthopaedics, The Second Hospital of Shandong University, 247 Beiyuan Street, Jinan, Shandong, 250033, People's Republic of China.
Guowei YangDepartment of Orthopaedics, The Second Hospital of Shandong University, 247 Beiyuan Street, Jinan, Shandong, 250033, People's Republic of China.
Yijun RongDepartment of Spinal Surgery, Zhongda Hospital, College of Medicine, Southeast University, NO.87 Ding Jia Qiao, Nanjing, Jiangsu, 210009, People's Republic of China.
Dongjin WuDepartment of Orthopaedics, The Second Hospital of Shandong University, 247 Beiyuan Street, Jinan, Shandong, 250033, People's Republic of China. doctorwdj@163.com.
Zengxin GaoDepartment of Spinal Surgery, Zhongda Hospital, College of Medicine, Southeast University, NO.87 Ding Jia Qiao, Nanjing, Jiangsu, 210009, People's Republic of China. zhongdaspinegzx@163.com.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundIntervertebral disc degeneration (IVDD) is a multifactorial disorder and a leading contributor to chronic low back pain (LBP), highlighting the need for novel therapeutic strategies. Recent studies indicate that ferroptosis, driven by oxidative stress, plays a key role in the loss of nucleus pulposus cells (NPCs) during IVDD. Vacuole membrane protein 1 (VMP1), a membrane-associated regulator of autophagy, is known to influence various cellular processes. However, its role in IVDD remains unclear. This study investigates the function of VMP1 in IVDD and the mechanisms involved.

methodsWe established a rat model of IVDD to investigate the correlation between VMP1 expression and ferroptosis during IVDD progression. In vitro, a ferroptosis model of NPCs was induced using tert-butyl hydroperoxide (TBHP) to examine the effects of VMP1 knockdown on NPC apoptosis, extracellular matrix (ECM) degradation, ferroptosis, PINK1/Parkin-dependent mitophagy, and mitochondrial function. Furthermore, cyclosporin A (CsA), a mitophagy inhibitor, was employed to explore the role and potential mechanisms of VMP1 overexpression in regulating PINK1/Parkin-mediated mitophagy, mitochondrial function, and ferroptosis.

resultsIn this study, we observed a significant downregulation of VMP1 expression in a rat model of IVDD, which was accompanied by the occurrence of ferroptosis. Subsequent experiments revealed that VMP1 knockdown aggravated apoptosis and ECM degradation in NPCs. Furthermore, we demonstrated that VMP1 silencing promoted ferroptosis, inhibited PINK1/Parkin-dependent mitophagy, and impaired mitochondrial function in NPCs. In contrast, VMP1 overexpression enhanced PINK1/Parkin-mediated mitophagy, mitigated mitochondrial dysfunction, and suppressed ferroptosis. Notably, these protective effects were abolished by treatment with CsA.

conclusionsThis study demonstrates that VMP1 alleviates IVDD by inhibiting ferroptosis and mitochondrial dysfunction in NPCs, a protective effect mediated through the promotion of PINK1/Parkin-dependent mitophagy. Our study underscores the pivotal role of VMP1 in coordinating mitophagy and ferroptosis during IVDD pathogenesis, identifying VMP1 as a potential therapeutic target for IVDD treatment.

Indexed as

FerroptosisIntervertebral Disc DegenerationMembrane ProteinsMitochondriaMitophagyNucleus PulposusProtein KinasesUbiquitin-Protein LigasesAnimalsCells, CulturedDisease Models, AnimalMalePTEN-Induced Putative KinaseRatsRats, Sprague-DawleySignal TransductionMembrane Proteinsparkin proteinProtein KinasesPTEN-Induced Putative KinaseUbiquitin-Protein LigasesFerroptosisIVDDMitochondrial dysfunctionMitophagyVMP1

Identifiers

PMID40629421
PMCPMC12239386

What Socratic holds

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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 Socratic graph.