Evidence map›Paper›PMID 42099639›Full record

ArticleFrontiers in immunology2026

Deciphering the regulatory mechanism and therapeutic potential of ECM degradation in intervertebral disc degeneration via multi-omics integration.

Lei Feng, Wei Zhong, Wenhua Liu, Xiang Guo, Leilei Wu

Abstract read
In one paragraph

Article in Frontiers in immunology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
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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

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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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

5 authors.

Lei Feng *Department of Joint Surgery, Affiliated Hospital of Shandong Second Medical University, Weifang, China.
Wei Zhong *Department of Joint Surgery, Affiliated Hospital of Shandong Second Medical University, Weifang, China.
Wenhua Liu *Department of Spinal Surgery, Affiliated Hospital of Shandong Second Medical University, Weifang, China.
Xiang Guo *Department of Spinal Surgery, Affiliated Hospital of Shandong Second Medical University, Weifang, China.
Leilei WuDepartment of Spinal Surgery, Affiliated Hospital of Shandong Second Medical University, Weifang, China.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Background: Intervertebral disc degeneration (IVDD) is a major cause of chronic low back pain, characterized not only by extracellular matrix (ECM) degradation but also by a chronic low-grade inflammatory response. The crosstalk between immune microenvironment dysregulation and protease-driven ECM breakdown remains poorly understood, hindering the development of targeted therapies. Methods: We integrated multiple transcriptomic datasets to map the landscape of ECM-degrading proteases in IVDD. Machine learning algorithms (LASSO, Random Forest, SVM) were employed to identify key regulatory genes. Their association with immune cell infiltration and inflammatory pathways was investigated. A diagnostic ridge regression model was constructed, and molecular docking was performed to screen for potential therapeutics. The top candidate, pravastatin sodium, was validated Results: MMP3 and ADAMTS1 were identified as core genes driving ECM degradation, and their expression was strongly correlated with the abundance of pro-inflammatory immune cells and activation of inflammatory pathways. The model based on these genes effectively distinguished degenerated discs. Single-cell analysis revealed that high-degradation nucleus pulposus cells exhibited enhanced pro-inflammatory intercellular communication and metabolic reprogramming towards a pro-inflammatory state. Molecular docking confirmed high binding affinity of pravastatin sodium to MMP3 and ADAMTS1. Experimental validation demonstrated that pravastatin sodium alleviated IVDD by reducing ECM degradation, suppressing pro-inflammatory cytokine (e.g., IL-1β) expression, and inhibiting apoptosis. Conclusion: Our study delineates a critical network linking ECM degradation to immune microenvironment activation in IVDD, with MMP3 and ADAMTS1 serving as central hubs. Pravastatin sodium emerges as a promising therapeutic agent capable of disrupting this pathogenic network, offering a novel immunomodulatory strategy for slowing disc degeneration.

Indexed as

Extracellular MatrixIntervertebral Disc DegenerationADAMTS1 ProteinAnimalsGene Expression ProfilingHumansMatrix Metalloproteinase 3Molecular Docking SimulationNucleus PulposusPravastatinADAMTS1 ProteinMatrix Metalloproteinase 3MMP3 protein, humanPravastatinextracellular matrix degradationimmune microenvironmentinflammationintervertebral disc degenerationmachine learningpravastatin sodium

Identifiers

PMID42099639
PMCPMC13143665

What Socratic 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 Socratic graph.