Evidence map›Paper›PMID 39993958›Full record

ArticleJournal of cellular and molecular medicine2025

ZIP8 Regulates Inflammation and Macrophage Polarisation in Intervertebral Disc Degeneration via the Wnt/β-Catenin Pathway.

Jun Xu, Huijie Gu, Kaifeng Zhou, Liang Wu, Yiming Zhang, Chong Bian, Zhongyue Huang, Guangnan Chen, Xiangyang Cheng, Xiaofan Yin

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of cellular and molecular medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed, 1 pooled it
–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

3 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Review
  3. Article
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.

Jun XuDepartment of Orthopaedics, Minhang Hospital, Fudan University, Shanghai, China.ORCID 0009-0003-8232-1405
Huijie GuDepartment of Orthopaedics, Minhang Hospital, Fudan University, Shanghai, China.
Kaifeng ZhouDepartment of Orthopaedics, Minhang Hospital, Fudan University, Shanghai, China.
Liang WuDepartment of Orthopaedics, Minhang Hospital, Fudan University, Shanghai, China.
Yiming ZhangDepartment of Orthopaedics, Minhang Hospital, Fudan University, Shanghai, China.
Chong BianDepartment of Orthopaedics, Minhang Hospital, Fudan University, Shanghai, China.
Zhongyue HuangDepartment of Orthopaedics, Minhang Hospital, Fudan University, Shanghai, China.
Guangnan ChenDepartment of Orthopaedics, Minhang Hospital, Fudan University, Shanghai, China.
Xiangyang ChengDepartment of Orthopaedics, Minhang Hospital, Fudan University, Shanghai, China.
Xiaofan YinDepartment of Orthopaedics, Minhang Hospital, Fudan University, Shanghai, China.

Funding

General Projects of Shanghai Municipal Health Commission 202040021
6 · The paper itself

Abstract

One main cause of persistent back discomfort is intervertebral disc degeneration (IDD), with inflammation and extracellular matrix (ECM) degradation playing critical roles. This study investigates the role of ZIP8, a zinc transporter, in IDD pathogenesis, focusing on its effects on inflammatory responses, ECM degradation and Wnt/β-catenin signalling pathway. ZIP8 was identified as a hub gene from the GSE27494 dataset through bioinformatics analysis. The role of ZIP8 was investigated in nucleus pulposus (NP) cells and RAW 264.7 macrophages. An in vivo IDD rat model was used to assess the consequences of ZIP8 overexpression. The involvement of the Wnt/β-catenin pathway was examined, and the effect on macrophage polarisation was analysed. ZIP8 overexpression in NP cells led to increased inflammatory cytokine production and enhanced NF-κB pathway activation, while ZIP8 knockdown alleviated these effects. In vitro, ZIP8 knockdown reduced IL-1β-induced apoptosis and ECM degradation, promoting cell viability. In vivo, ZIP8 overexpression exacerbated disc degeneration, as evidenced by magnetic resonance imaging (MRI) and histological assessments. Additionally, modulation of ZIP8, in conjunction with the Wnt/β-catenin signalling pathway, revealed its involvement in regulating apoptosis and proliferation in NP cells. In RAW 264.7 macrophages, ZIP8 knockdown inhibited M1 macrophage polarisation and reduced proinflammatory cytokine expression, while promoting anti-inflammatory responses. ZIP8 is a key regulator in IDD, affecting inflammation, ECM integrity and Wnt/β-catenin signalling pathways. Targeting ZIP8 by knockdown may offer therapeutic potential in IDD by modulating inflammatory responses and protecting ECM structure, offering a novel approach to IDD treatment.

Indexed as

Cation Transport ProteinsInflammationIntervertebral Disc DegenerationMacrophagesWnt Signaling PathwayAnimalsApoptosisCytokinesDisease Models, AnimalExtracellular MatrixHumansMaleMiceNucleus PulposusRatsRats, Sprague-DawleyCation Transport ProteinsCytokinesinflammationintervertebral disc degenerationM1 macrophage polarisationWnt/β‐catenin signalling pathwayZIP8

Identifiers

PMID39993958
PMCPMC11850097

What OpenQuestion holds

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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.