ArticleThe Journal of biological chemistry2011
TNF-α and IL-1β promote a disintegrin-like and metalloprotease with thrombospondin type I motif-5-mediated aggrecan degradation through syndecan-4 in intervertebral disc.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 164 papers.
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Who cites it
164 citing papers in PubMed, 259 citations in OpenAlex.
- Inflammatory cytokines induce NOTCH signaling in nucleus pulposus cells: implications in intervertebral disc degeneration.The Journal of biological chemistry · 2013Trial
- Identification and Experimental Validation of PANoptosis Key Genes for Constructing a PANoptosis Risk Diagnostic Model in Intervertebral Disc Degeneration.The journal of gene medicine · 2026Article
- Ergothioneine-Derived Carbon Dot Nanozymes Alleviate the Oxidative Stress Microenvironment to Delay Intervertebral Disc Degeneration.Antioxidants (Basel, Switzerland) · 2026Article
- Current research on the role of HIF in intervertebral disc degeneration.European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society · 2026Review
- A manganese-luteolin co-loaded antioxidant hydrogel for synergistic alleviation of oxidative stress and immunomodulation in intervertebral disc degeneration.Materials today. Bio · 2026Article
- Restoring disc matrix homeostasis: Dual-miRNA and human platelet lysate as a novel therapeutic strategy.Materials today. Bio · 2026Article
- Comparative Analysis of Dual-miRNA Mediated Stimulation of Nucleus Pulposus and Bone Marrow Derived Stem Cells for Intervertebral Disc Repair.JOR spine · 2026Article
- Advances in the study of macrophage polarization in intervertebral disc degeneration.European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society · 2026Review
- Circular RNAs in intervertebral disc degeneration: Current insights into mechanisms and therapeutic potentials (Review).Molecular medicine reports · 2026Review
- GOLGB1 deficiency accelerates intervertebral disc degeneration by activating the MAPK pathway.Scientific reports · 2026Article
- SMR Analysis Integrating GWAS and eQTL Data Reveals UHRF1BP1 and SNRPC as Potential Drug Targets for Low Back Pain.Journal of pain research · 2026Article
- Cellular and molecular mechanisms of diabetes-mediated disc degeneration.Frontiers in endocrinology · 2026Review
- Deciphering the regulatory mechanism and therapeutic potential of ECM degradation in intervertebral disc degeneration via multi-omics integration.Frontiers in immunology · 2026Article
- Review
- Photothermal-triggered NO-releasing nanofiber membrane mitigates intervertebral disc degeneration via inflammation inhibition and matrix stabilization.Materials today. Bio · 2025Article
- SDC4 drives fibrotic remodeling of the intervertebral disc under altered spinal loading.Cell death & disease · 2025Article
- Clinical Efficacy and Risks of Intradiscal Orthobiological Injections: A Narrative Review.Current pain and headache reports · 2025Review
- Regenerative strategies for intervertebral disc degeneration.Journal of orthopaedic translation · 2025Review
- Drug screen reveals new potent host-targeted antivirals against Mpox virus.Research square · 2025Article
- An Extracellular Matrix Hydrogel Restores Disc Volume and Alleviates Axial Hypersensitivity in a Rat Model of Disc-Associated Pain.JOR spine · 2025Article
104 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
Elevated levels of TNF-α, IL-1β and a resultant increase in ADAMTS (a disintegrin-like and metalloprotease with thrombospondin type I motifs) expression is seen during disc degeneration. However, if these pro-inflammatory cytokines control ADAMTS activity is not definitively known. The goal of the investigation was to study if TNF-α and IL-1β regulate syndecan-4 (SDC4) expression, and if SDC4 was responsible for promoting aggrecan degradation through controlling ADAMTS activity in nucleus pulposus cells of the intervertebral disc. Cytokine treatment increased SDC4 expression and promoter activity. Use of inhibitor, SM7368 and co-transfections with IκBα, RelA/p50 showed that NF-κΒ regulated both basal and cytokine-dependent SDC4 transcription. SDC4 promoter harboring RelA binding site mutation was unresponsive to the cytokines. Moreover, cytokines failed to increase SDC4 promoter activity in RelA-null cells. Cytokines increased ADAMTS-4/5 expression and aggrecan degradation and promoted SDC4 interaction with ADAMTS-5. Treatment with heparinase-III and p-nitrophenyl-β-D-xylopyranoside (PNPX), an inhibitor of heparan sulfate synthesis and transfection with SDC4-shRNA partially blocked cytokine mediated aggrecan degradation. Analysis of human tissues showed increased aggrecan degradation with a concomitant increase in SDC4 and ADAMTS-5 protein expression with severity of disc disease. Likewise, SDC4, TNF-α, IL-1β, ADAMTS-4, and ADAMTS-5 mRNA expression increased in degenerate tissues. We conclude that in nucleus pulposus, TNF-α and IL-1β regulate SDC4 expression, which plays a key role in pathogenesis of degenerative disc disease by promoting aggrecan degradation by ADAMTS-5.
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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.