Evidence map›Paper›PMID 39052181›Full record

ArticleInflammation2025

EZH2-H3K27me3-Mediated Epigenetic Silencing of DKK1 Induces Nucleus Pulposus Cell Pyroptosis in Intervertebral Disc Degeneration by Activating NLRP3 and NAIP/NLRC4.

Qijun Yao, Yue Lei, Yongxu Zhang, Haoran Chen, Xiaowei Dong, Zhiqiang Ye, Haidong Liang

Abstract read
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In one paragraph

Article in Inflammation, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
–field-weighted citation impact
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

10 citing papers in PubMed.

  1. Article
  2. Review
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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

7 authors.

Qijun Yao *Department of Bone and Soft Tissue Repair and Reconstructive Surgery, The Second Hospital of Dalian Medical University, No. 467 Zhongshan Road, Dalian, Liaoning, 116000, China.
Yue Lei *Department of Bone and Soft Tissue Repair and Reconstructive Surgery, The Second Hospital of Dalian Medical University, No. 467 Zhongshan Road, Dalian, Liaoning, 116000, China.
Yongxu ZhangDepartment of Bone and Soft Tissue Repair and Reconstructive Surgery, The Second Hospital of Dalian Medical University, No. 467 Zhongshan Road, Dalian, Liaoning, 116000, China.
Haoran ChenDepartment of Bone and Soft Tissue Repair and Reconstructive Surgery, The Second Hospital of Dalian Medical University, No. 467 Zhongshan Road, Dalian, Liaoning, 116000, China.
Xiaowei DongDepartment of Bone and Soft Tissue Repair and Reconstructive Surgery, The Second Hospital of Dalian Medical University, No. 467 Zhongshan Road, Dalian, Liaoning, 116000, China.
Zhiqiang YeDepartment of Bone and Soft Tissue Repair and Reconstructive Surgery, The Second Hospital of Dalian Medical University, No. 467 Zhongshan Road, Dalian, Liaoning, 116000, China.
Haidong LiangDepartment of Bone and Soft Tissue Repair and Reconstructive Surgery, The Second Hospital of Dalian Medical University, No. 467 Zhongshan Road, Dalian, Liaoning, 116000, China. johnlhddmu@outlook.com.ORCID http://orcid.org/0009-0003-0085-2449

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Nucleus pulposus (NP) cell pyroptosis is crucial for intervertebral disc degeneration (IDD). However, the precise mechanisms underlying pyroptosis in IDD remain elusive. Therefore, this study aimed to investigate how dickkopf-1 (DKK1) influences NP cell pyroptosis and delineate the regulatory mechanisms of IDD. Behavioral tests and histological examinations were conducted in rat IDD models to assess the effect of DKK1 on the structure and function of intervertebral discs. Detected pyroptosis levels using Hoechst 33,342/propidium iodide (PI) double staining, and determined pyroptosis-related protein expression via western blotting. The cellular mechanisms of DKK1 in pyroptosis were explored in interleukin (IL)-1β-induced NP cells transfected with or without DKK1 overexpression plasmids (oe-DKK1). In addition, IL-1β-treated NP cells transfected with sh-EZH2 and/or sh-DKK1 were utilized to clarify the interplay between the enhancer of zeste homologue 2 (EZH2) and DKK1 in pyroptosis. Additionally, the epigenetic regulation of DKK1 by EZH2 was explored in NP cells treated with the EZH2 inhibitors GSK126/DZNep. DKK1 expression decreased in IDD rats. Transfection with oe-DKK1 reduced pro-inflammatory factors and extracellular matrix markers in IDD rats. In IL-1β-induced NP cells, DKK1 overexpression suppressed pyroptosis and inhibited the NLRP3 and NAIP/NLRC4 inflammasome activation. EZH2 knockdown increased DKK1 expression and reduced pyroptosis-related proteins. Conversely, DKK1 downregulation reversed the inhibitory effects of EZH2 knockdown on pyroptosis. Furthermore, EZH2 suppressed DKK1 expression via H3K27 methylation at the DKK1 promoter. EZH2 negatively regulates DKK1 expression via H3K27me3 methylation, promoting NP cell pyroptosis in IDD patients. This regulatory effect involves the activation of NLRP3 and NAIP/NLRC4 inflammasomes.

Indexed as

Enhancer of Zeste Homolog 2 ProteinEpigenesis, GeneticHistonesIntercellular Signaling Peptides and ProteinsIntervertebral Disc DegenerationNLR Family, Pyrin Domain-Containing 3 ProteinNucleus PulposusPyroptosisAnimalsGene SilencingHumansMaleRatsRats, Sprague-DawleyDkk1 protein, ratEnhancer of Zeste Homolog 2 ProteinEZH2 protein, ratHistonesIntercellular Signaling Peptides and ProteinsNLR Family, Pyrin Domain-Containing 3 ProteinNlrp3 protein, ratDickkopf1Enhancer of zeste homologue 2Histone methylationInflammasomesIntervertebral disc degenerationPyroptosis

Identifiers

PMID39052181

What OpenQuestion holds

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Read underepoch 390

Registered trials

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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.