Evidence mapPaperPMID 41511606Full record

ArticleApplied biochemistry and biotechnology2026

TEAD4 and RXRA Regulate the Function of Nucleus Pulposus Cells in Intervertebral Disc Degeneration Via the TNF-α/NF-κB Pathway: An Integrated Analysis of Single-Cell RNA-Seq, Bulk RNA-Seq, and In Vitro Validation.

Liang Yang, Hui Liu, Jian Pu, Yang Hu, Yajun Deng, Xiongwei Yan, Mingxuan Liu

Abstract read
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Article in Applied biochemistry and biotechnology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

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2 · The registry

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

7 authors.

Liang Yang *Department of Orthopedics, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang, Hubei, 441021, China.
Hui Liu *Department of Neurology, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang, Hubei, 441021, China.
Jian PuDepartment of Orthopedics, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang, Hubei, 441021, China.
Yang HuDepartment of Orthopedics, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang, Hubei, 441021, China.
Yajun DengDepartment of Orthopedics, Xi'an Daxing Hospital, Xi'an, Shaanxi, 710000, China.ORCID http://orcid.org/0000-0003-0953-6525
Xiongwei YanDepartment of Orthopedics, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang, Hubei, 441021, China. 415607947@qq.com.
Mingxuan LiuDepartment of Orthopedics, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang, Hubei, 441021, China. 157342993@qq.com.

Funding

National Natural Sciences Foundation of China 82260443Natural Science Basic Research of Shaanxi Province 2024JC-YBQN-0924Xiangyang Central Hospital Institute level Scientific Research Project 2023YB08
6 · The paper itself

Abstract

Intervertebral disc degeneration (IDD) is a major risk factor for chronic low back pain, but the mechanisms driving its progression remain unclear. To address this gap, we integrated single-cell RNA sequencing (scRNA-seq) and bulk RNA sequencing analyses, combined with in vitro experiments, to investigate the roles of key transcription factors (TFs) in IDD. First, we analyzed the scRNA-seq dataset GSE244889 and bulk RNA dataset GSE15227. Using marker gene analysis, we identified eight cell clusters in nucleus pulposus (NP) tissues. Gene Set Enrichment Analysis (GSEA) was applied to both datasets to screen for enriched TFs: 20 TFs were identified in GSE244889 and 42 in GSE15227. Intersection of these results yielded 12 common TFs, including TEAD4 and RXRA. To validate these TFs, we established an interleukin-1β-induced senescent NP cell model and performed RT-qPCR. Results showed that FOSL2, HSF1, CEBPB, RXRA, and ESR1 were upregulated, while GATA3, TEAD4, JUN, FOXM1, and JUND were downregulated in senescent NP cells. Immunohistochemical staining of human NP tissues further revealed that RXRA expression was increased and TEAD4 expression was decreased in late-stage IDD compared to early-stage IDD. Correlation analysis demonstrated that RXRA was negatively correlated with Collagen II and positively correlated with matrix metalloproteinase 3, whereas TEAD4 showed the opposite correlation pattern. Additionally, GSEA and Kyoto Encyclopedia of Genes and Genomes pathway analysis indicated that the tumor necrosis factor-α/nuclear factor-κB (TNF-α/NF-κB) pathway was enriched in IDD. In conclusion, TEAD4 and RXRA play critical roles in IDD progression, likely by regulating NP cell behavior and extracellular matrix metabolism through the TNF-α/NF-κB pathway. These findings provide novel insights for developing targeted therapies for IDD.

Indexed as

DNA-Binding ProteinsIntervertebral Disc DegenerationMuscle ProteinsNF-kappa BNucleus PulposusRNA-SeqSignal TransductionTranscription FactorsTumor Necrosis Factor-alphaHumansSingle-Cell AnalysisTEA Domain Transcription FactorsDNA-Binding ProteinsMuscle ProteinsNF-kappa BTEAD4 protein, humanTEA Domain Transcription FactorsTranscription FactorsTumor Necrosis Factor-alphaIntervertebral disc degenerationSingle-cell RNA sequencingTNF-α/NF-κB pathwayTranscription factor

Identifiers

PMID41511606
PMCPMC12995935

What Socratic holds

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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.