ArticleScientific reports2017
Toll-like Receptor Activation Induces Degeneration of Human Intervertebral Discs.
Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 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.
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Who cites it
41 citing papers in PubMed, 63 citations in OpenAlex.
- Management of Musculoskeletal Injuries with an Inflammatory Damage-Associated Molecular Pattern (DAMP) Etiology.Pain and therapy · 2026Review
- Aggrecan and small leucine-rich proteoglycan fragments correlate with Toll-like receptor-2 mediated inflammation in painful degenerative disc disease.The Korean journal of pain · 2026Article
- Extracellular matrix fragments and Toll-like receptor-2: reinforcing the mechanistic bridge from disc degeneration to inflammation in human tissue.The Korean journal of pain · 2026Article
- Article
- A multifactorial intervertebral disc degeneration model: Integrating inflammation, structural disruption, biomechanical parameters, and neural sensitization.Bioengineering & translational medicine · 2026Article
- Beyond miRNA Cargo Profiles: Anti-Inflammatory Roles of Extracellular Vesicle-Enriched miRNAs Derived From Human Intervertebral Disc Cells Unveiled by Functional Testing.Journal of extracellular biology · 2026Article
- Potential Role of Mast Cells in Intervertebral Disc Ageing, Herniation Resolution, and Degeneration: Evidence and Lessons Learned from Studies of Mast Cells in Other Connective Tissues.International journal of molecular sciences · 2026Review
- Stress-response exhaustion in intervertebral disc degeneration.Frontiers in cell and developmental biology · 2026Review
- Intracellular Detection ofJOR spine · 2025Article
- GATA6 Facilitates Progression of Intervertebral Disc Degeneration by Regulating Ferroptosis via Targeting TLR2/AKR1C3.International journal of biological sciences · 2025Article
- The role of miR-155-5p in inflammation and mechanical loading during intervertebral disc degeneration.Cell communication and signaling : CCS · 2024Article
- Article
- Review
- Plant-Derived Senotherapeutics for the Prevention and Treatment of Intervertebral Disc Degeneration and Aging.Metabolites · 2024Review
- Sex differences in the biomechanical and biochemical responses of caudal rat intervertebral discs to injury.JOR spine · 2023Article
- Article
- An Immune-Related Gene Signature for Predicting Survival and Immunotherapy Efficacy in Esophageal Adenocarcinoma.Medical science monitor : international medical journal of experimental and clinical research · 2023Article
- Senolytic Combination Treatment Is More Potent Than Single Drugs in Reducing Inflammatory and Senescence Burden in Cells from Painful Degenerating IVDs.Biomolecules · 2023Article
- Toll-like receptor 4 signaling in osteoblasts is required for load-induced bone formation in mice.iScience · 2023Article
- Cellular Senescence in Intervertebral Disc Aging and Degeneration: Molecular Mechanisms and Potential Therapeutic Opportunities.Biomolecules · 2023Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Toll-like receptors (TLR) are activated by endogenous alarmins such as fragmented extracellular matrix compounds found in the degenerating disc. TLRs regulate cytokine, neurotrophin, and protease expression in human disc cells in vitro, and thus control key factors in disc degeneration. However, whether TLR activation leads to degenerative changes in intact human discs is unclear. Nucleus pulposus (NP) cells isolated from non-degenerating discs increase IL-1β and nerve growth factor gene expression following treatment with Pam2CSK4 (TLR2/6 agonist) but not Pam3CSK4 (TLR1/2 agonist). Challenging NP cells with Pam2CSK4 or 30 kDa fibronectin fragments (FN-f, an endogenous TLR2 and TLR4 alarmin) increased secretion of proinflammatory cytokines. We then investigated the effect of TLR activation in intact, non-degenerate, ex vivo human discs. Discs were injected with PBS, Pam2CSK4 and FN-f, and cultured for 28 days. TLR activation increased proteoglycan and ECM protein release into the culture media and decreased proteoglycan content in the NP. Proteases, including MMP3, 13 and HTRA1, are secreted at higher levels following TLR activation. In addition, proinflammatory cytokine levels, including IL-6, TNFα and IFNγ, increased following TLR activation. These results indicate that TLR activation induces degeneration in human discs. Therefore, TLRs are potential disease-modifying therapeutic targets to slow disc degeneration.
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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.