Trial reportThe Journal of biological chemistry2013
Inflammatory cytokines induce NOTCH signaling in nucleus pulposus cells: implications in intervertebral disc degeneration.
Trial report in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 77 papers.
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.
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.
Who cites it
77 citing papers in PubMed, 114 citations in OpenAlex.
- Correlation of EYS polymorphisms with lumbar disc herniation risk among Han Chinese population.Molecular genetics & genomic medicine · 2019Trial
- Article
- Article
- A ROS and pH dual - responsive hydrogel-nanoparticle system restores intervertebral disc and alleviates related pain by modulating senescence and panoptosis of nucleus pulposus cells.Materials today. Bio · 2026Article
- Sex Hormones Attenuate Pro-Inflammatory Gene Expression in Nucleus Pulposus and Annulus Fibrosus Cells in a Cell-Type Specific Manner.JOR spine · 2026Article
- Integrative analysis of single-cell RNA sequencing, bulk RNA sequencing, and proteomic data identified NOTCH3 as a hub gene contributing to human intervertebral disc fibrosis.Scientific reports · 2026Article
- Review
- Review
- The Role of Notch Signaling and Gut Microbiota in Autoinflammatory Diseases: Mechanisms and Future Views.Biomedicines · 2025Review
- Therapeutic potential of targeting the IRF2/POSTN/Notch1 axis in nucleus pulposus cells for intervertebral disc degeneration.Journal of neuroinflammation · 2025Article
- Demyelination and Remyelination: General Principles.Advances in neurobiology · 2025Review
- Immune microenvironment in intervertebral disc degeneration: pathophysiology and therapeutic potential.Frontiers in immunology · 2025Review
- Targeting nucleus pulposus cell death in the treatment of intervertebral disc degeneration.JOR spine · 2024Review
- Bone Marrow Mesenchymal Stem Cell-Derived Exosomes Alleviate Nuclear Pulposus Cells Degeneration Through the miR-145a-5p/USP31/HIF-1α Signaling Pathway.Stem cell reviews and reports · 2024Article
- APOE-NOTCH axis governs elastogenesis during human cardiac valve remodeling.Nature cardiovascular research · 2024Article
- Therapeutic effect and mechanism of Yougui Wan in rats with intervertebral disk degeneration.Journal of orthopaedic surgery and research · 2024Article
- Potential susceptibility genes in patients with stage III and IV periodontitis: A whole-exome sequencing pilot study.Biomolecules & biomedicine · 2024Article
- The marine Penicillium sp. GGF16-1-2 metabolite dicitrinone G inhibits pancreatic angiogenesis by regulating the activation of NLRP3 inflammasome.Journal of natural medicines · 2024Article
- Machine learning-based diagnostic model of lymphatics-associated genes for new therapeutic target analysis in intervertebral disc degeneration.Frontiers in immunology · 2024Article
- Updates on Pathophysiology of Discogenic Back Pain.Journal of clinical medicine · 2023Review
17 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 4 institutions in 3 countries.
Funding
Abstract
The objective of the study was to investigate how inflammatory cytokines, IL-1β, and TNF-α control NOTCH signaling activity in nucleus pulposus (NP) cells. An increase in expression of selective NOTCH receptors (NOTCH1 and -2), ligand (JAGGED2), and target genes (HES1, HEY1, and HEY2) was observed in NP cells following cytokine treatment. A concomitant increase in NOTCH signaling as evidenced by induction in activity of target gene HES1 and HEY1 promoters and reporter 12xCSL was seen. Moreover, treatment increased activity of a 2-kb NOTCH2 promoter. Treatment of cells with NF-κB and MAPK inhibitors abolished the inductive effect of cytokines on NOTCH2 promoter and its expression. Gain and loss-of-function studies confirmed the inductive effect of p65 on NOTCH2 promoter activity. In contrast, p50 blocked the cytokine induction of promoter activity. Supporting promoter studies, lentiviral delivery of sh-p65, and sh-IKKβ significantly decreased cytokine dependent change in NOTCH2 expression. Interestingly, MAPK signaling showed an isoform-specific control of NOTCH2 promoter; p38α/β2/δ, ERK1, and ERK2 contributed to cytokine dependent induction, whereas p38γ played no role. Analysis of human NP tissues showed that NOTCH1 and -2 and HEY2 expression correlated with each other. Moreover, expression of NOTCH2 and IL-1β as well as the number of cells immunopositive for NOTCH2 significantly increased in histologically degenerate discs compared with non-degenerate discs. Taken together, these results explain the observed dysregulated expression of NOTCH genes in degenerative disc disease. Thus, controlling IL-1β and TNF-α activities during disc disease may restore NOTCH signaling and nucleus pulposus cell function.
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Registered trials
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.