ArticleBone research2020
Melatonin alleviates intervertebral disc degeneration by disrupting the IL-1β/NF-κB-NLRP3 inflammasome positive feedback loop.
Article in Bone research, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 143 papers.
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Who cites it
143 citing papers in PubMed, 240 citations in OpenAlex.
- A nucleic acid regulation strategy under mechanical stress for intervertebral disc degeneration treatment.Bioactive materials · 2026Article
- The role of sleep and circadian rhythms 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
- MnOMaterials today. Bio · 2026Article
- Identification and Experimental Validation of Key Genes Related to Neuroendocrine in Periodontitis Based on Single-Cell and Bulk Transcriptome Data.Journal of cellular and molecular medicine · 2026Article
- 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
- Macrophage-derived legumain ameliorates excessive mechanical stress-induced ferroptosis of nucleus pulposus cells and intervertebral disc degeneration via integrin αvβ3-Hippo signaling.Cellular & molecular biology letters · 2026Article
- HACE1 alleviates intervertebral disc degeneration by inhibiting ferroptosis in nucleus pulposus cells.Scientific reports · 2026Article
- PTPN22 as a therapeutic target in intervertebral disc degeneration: Modulating mitophagy and pyroptosis through the PI3K/AKT/mTOR axis.Journal of advanced research · 2026Article
- Pyroptosis: mechanism and therapeutic strategies with intervertebral disc degeneration.Experimental & molecular medicine · 2026Review
- Acetylation Regulates ACSL4 Degradation Through Chaperone-Mediated Autophagy to Alleviate Intervertebral Disc Degeneration.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Cellular and molecular mechanisms of diabetes-mediated disc degeneration.Frontiers in endocrinology · 2026Review
- Melatonin is associated with cell-type-specific inflammatory and oxidative stress responses at the maternal-fetal interface.Frontiers in immunology · 2026Article
- METTL3-Mediated m6A Modification of lncRNA-0949 Drives Microglial Inflammation in an vitro Model of Sepsis-Associated Encephalopathy.Journal of inflammation research · 2026Article
- SR9009 regulates macrophage polarization via the NR1D1/NF-κB axis to ameliorate obesity-associated ulcerative colitis.Frontiers in gastroenterology (Lausanne, Switzerland) · 2026Article
- Review
- Obesity-induced NLRP3 inflammasome activation in nucleus pulposus cells accelerates intervertebral disk degeneration.Journal of orthopaedic surgery and research · 2025Article
- Prenatal alcohol exposure promotes nerve injury-induced pathological pain following morphine treatment via NLRP3-mediated peripheral and central proinflammatory immune actions.Brain, behavior, and immunity · 2025Article
- (Z)-Ligustilide alleviates intervertebral disc degeneration by suppressing nucleus pulposus cell pyroptosis via Atg5/NLRP3 axis.Science China. Life sciences · 2025Article
- Controlled releasing melatonin nanoparticles promote restoration of nucleus pulposus cell homeostasis for alleviating intervertebral disc degeneration.Materials today. Bio · 2025Article
- Comparative Analysis of Melatonin and Polydeoxyribonucleotide: Possible Benefits of Co-Treatment Effects and Potential Synergistic Applicability.International journal of molecular sciences · 2025Review
83 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The inflammatory response is induced by the overexpression of inflammatory cytokines, mainly interleukin (IL)-1β, and is one of the main causes of intervertebral disc degeneration (IVDD). NLR pyrin domain containing 3 (NLRP3) inflammasome activation is an important source of IL-1β. As an anti-inflammatory neuroendocrine hormone, melatonin plays various roles in different pathophysiological conditions. However, its roles in IVDD are still not well understood and require more examination. First, we demonstrated that melatonin delayed the progression of IVDD and relieved IVDD-related low back pain in a rat needle puncture IVDD model; moreover, NLRP3 inflammasome activation (NLRP3, p20, and IL-1β levels) was significantly upregulated in severely degenerated human discs and a rat IVDD model. Subsequently, an IL-1β/NF-κB-NLRP3 inflammasome activation positive feedback loop was found in nucleus pulposus (NP) cells that were treated with IL-1β. In these cells, expression of NLRP3 and p20 was significantly increased, NF-κB signaling was involved in this regulation, and mitochondrial reactive oxygen species (mtROS) production increased. Furthermore, we found that melatonin disrupted the IL-1β/NF-κB-NLRP3 inflammasome activation positive feedback loop in vitro and in vivo. Melatonin treatment decreased NLRP3, p20, and IL-1β levels by inhibiting NF-κB signaling and downregulating mtROS production. Finally, we showed that melatonin mediated the disruption of the positive feedback loop of IL-1β in vivo. In this study, we showed for the first time that IL-1β promotes its own expression by upregulating NLRP3 inflammasome activation. Furthermore, melatonin disrupts the IL-1β positive feedback loop and may be a potential therapeutic agent for IVDD.
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