ArticleThe American journal of pathology2013
Inflammatory cytokines associated with degenerative disc disease control aggrecanase-1 (ADAMTS-4) expression in nucleus pulposus cells through MAPK and NF-κB.
Article in The American journal of pathology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 126 papers.
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Who cites it
126 citing papers in PubMed, 184 citations in OpenAlex.
- Inflammatory cytokines induce NOTCH signaling in nucleus pulposus cells: implications in intervertebral disc degeneration.The Journal of biological chemistry · 2013Trial
- Hepatic p38γ exacerbates acetaminophen‑induced acute liver injury via PI3K/Akt‑dependent mechanisms.International journal of molecular medicine · 2026Article
- Lumbar degenerative disease: association of serum complement levels with diagnosis, structural severity, and postoperative prognosis.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 · 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
- ADAMTS4 elicits myeloid-derived immune cell recruitment and liver fibrogenesis in metabolic dysfunction-associated steatotic liver disease.Signal transduction and targeted therapy · 2026Article
- The Role of Piezo 1 in the Study of Intervertebral Disc Degeneration: Phenotype, Mechanism and Treatment.Orthopaedic surgery · 2026Review
- Adamts4 coordinates the transcriptomic profile of primary rat costal chondrocytes.Stem cells translational medicine · 2026Article
- TNF-α orchestrates ADAM metallopeptidase with thrombospondin type 1 motif 2 upregulation and extracellular matrix remodeling through multimodal signaling in osteosarcoma cells.Molecular biology reports · 2026Article
- Cellular and molecular mechanisms of diabetes-mediated disc degeneration.Frontiers in endocrinology · 2026Review
- Review
- Clinical-transcriptomic classification of lumbar disc degeneration enhanced by machine learning.Military Medical Research · 2025Article
- Current Mechanobiological Pathways and Therapies Driving Spinal Health.Bioengineering (Basel, Switzerland) · 2025Review
- Skeletal stem cells, a new direction for the treatment of bone and joint diseases.World journal of orthopedics · 2025Review
- An Extracellular Matrix Hydrogel Restores Disc Volume and Alleviates Axial Hypersensitivity in a Rat Model of Disc-Associated Pain.JOR spine · 2025Article
- Heme oxygenase 1‑overexpressing bone marrow mesenchymal stem cell‑derived exosomes suppress interleukin‑1 beta‑induced apoptosis and aging of nucleus pulposus cells.Molecular medicine reports · 2025Article
- Pyroptosis: A spoiler of peaceful coexistence between cells in degenerative bone and joint diseases.Journal of advanced research · 2025Review
- STAT-3, ELK-1, and c- Jun contributes IL-6 mediated ADAMTS-8 upregulation in colorectal cancer.Molecular biology reports · 2025Article
- Hippo-PKCζ-NFκB signaling axis: A druggable modulator of chondrocyte responses to mechanical stress.iScience · 2024Article
- Phillyrin reduces ROS production to alleviate the progression of intervertebral disc degeneration by inhibiting NF-κB pathway.Journal of orthopaedic surgery and research · 2024Article
- Lumbar intervertebral disc degeneration in low back pain.Minerva anestesiologica · 2024Review
66 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 3 institutions in 3 countries.
Funding
Abstract
We investigated TNF-α and IL-1β regulation of ADAMTS-4 expression in nucleus pulposus (NP) cells and its role in aggrecan degradation. Real-time quantitative RT-PCR, Western blotting, and transient transfections with rat NP cells and lentiviral silencing with human NP cells were performed to determine the roles of MAPK and NF-κB in cytokine-mediated ADAMTS-4 expression and function. ADAMTS4 expression and promoter activity increased in NP cells after TNF-α and IL-1β treatment. Treatment of cells with MAPK and NF-κB inhibitors abolished the inductive effect of the cytokines on ADAMTS4 mRNA and protein expression. Although ERK1, p38α, p38β2, and p38γ were involved in induction, ERK2 and p38δ played no role in TNF-α-dependent promoter activity. The inductive effect of p65 on ADAMTS4 promoter was confirmed through gain and loss-of-function studies. Cotransfection of p50 completely blocked p65-mediated induction. Lentiviral transduction with shRNA plasmids shp65, shp52, shIKK-α, and shIKK-β significantly decreased TNF-α-dependent increase in ADAMTS-4 and -5 levels and aggrecan degradation. Silencing of either ADAMTS-4 or -5 resulted in reduction in TNF-α-dependent aggrecan degradation in NP cells. By controlling activation of MAPK and NF-κB signaling, TNF-α and IL-1β modulate expression of ADAMTS-4 in NP cells. To our knowledge, this is the first study to show nonredundant contribution of both ADAMTS-4 and ADAMTS-5 to aggrecan degradation in human NP cells in vitro.
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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.