ArticleThe Journal of biological chemistry2016
Nerve Growth Factor Is Regulated by Toll-Like Receptor 2 in Human Intervertebral Discs.
Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 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
40 citing papers in PubMed, 65 citations in OpenAlex.
- Technical insights and implications of thoracolumbar spine and neural tissue harvesting in recently deceased organ donors: a direct anterior approach integrated into multi-organ procurement protocols.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
- Quantitative discometry: Low-dose concordant pain onset identifies sensitized annular nociceptors under pressure-volume-controlled provocation.Interventional pain medicine · 2026Article
- Iron, lipid peroxidation and discogenic pain: a redox framework for ferroptosis in intervertebral disc degeneration.Frontiers in cell and developmental biology · 2026Review
- What a pain in the back: etiology, diagnosis and future treatment directions for discogenic low back pain.Bone research · 2025Review
- Spinal implant wear particles: Generation, characterization, biological impacts, and future considerations.iScience · 2025Review
- Unveiling immune mechanisms and potential biomarkers in intervertebral disc degeneration through integrated analysis.Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologica · 2025Article
- The role of miR-155-5p in inflammation and mechanical loading during intervertebral disc degeneration.Cell communication and signaling : CCS · 2024Article
- Review
- Toll-like receptor 4 signaling in osteoblasts is required for load-induced bone formation in mice.iScience · 2023Article
- Degenerative Disc Disease of the Spine: From Anatomy to Pathophysiology and Radiological Appearance, with Morphological and Functional Considerations.Journal of personalized medicine · 2022Review
- Gene co-expression architecture in peripheral blood in a cohort of remitted first-episode schizophrenia patients.Schizophrenia (Heidelberg, Germany) · 2022Article
- An in vitro 3D annulus fibrosus cell culture model with type I collagen: An examination of cell-matrix interactions.JOR spine · 2022Article
- Localization of Nerve Growth Factor Expression to Structurally Damaged Cartilaginous Tissues in Human Lumbar Facet Joint Osteoarthritis.Frontiers in immunology · 2022Article
- Suramin attenuates intervertebral disc degeneration by inhibiting NF-κB signalling pathway.Bone & joint research · 2021Article
- Article
- Toll-like receptor 2 induced senescence in intervertebral disc cells of patients with back pain can be attenuated by o-vanillin.Arthritis research & therapy · 2021Article
- Pro-Inflammatory and Neurotrophic Factor Responses of Cells Derived from Degenerative Human Intervertebral Discs to the Opportunistic PathogenInternational journal of molecular sciences · 2021Article
- Painful intervertebral disc degeneration and inflammation: from laboratory evidence to clinical interventions.Bone research · 2021Review
- Multiscale Regulation of the Intervertebral Disc: Achievements in Experimental, In Silico, and Regenerative Research.International journal of molecular sciences · 2021Review
- Toll-like receptor involvement in adolescent scoliotic facet joint degeneration.Journal of cellular and molecular medicine · 2020Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 3 countries.
Funding
Abstract
Nerve growth factor (NGF) contributes to the development of chronic pain associated with degenerative connective tissue pathologies, such as intervertebral disc degeneration and osteoarthritis. However, surprisingly little is known about the regulation of NGF in these conditions. Toll-like receptors (TLR) are pattern recognition receptors classically associated with innate immunity but more recently were found to be activated by endogenous alarmins such as fragmented extracellular matrix proteins found in degenerating discs or cartilage. In this study we investigated if TLR activation regulates NGF and which signaling mechanisms control this response in intervertebral discs. TLR2 agonists, TLR4 agonists, or IL-1β (control) treatment increased NGF, brain-derived neurotrophic factor (BDNF), and IL-1β gene expression in human disc cells isolated from healthy, pain-free organ donors. However, only TLR2 activation or IL-1β treatment increased NGF protein secretion. TLR2 activation increased p38, ERK1/2, and p65 activity and increased p65 translocation to the cell nucleus. JNK activity was not affected by TLR2 activation. Inhibition of NF-κB, and to a lesser extent p38, but not ERK1/2 activity, blocked TLR2-driven NGF up-regulation at both the transcript and protein levels. These results provide a novel mechanism of NGF regulation in the intervertebral disc and potentially other pathogenic connective tissues. TLR2 and NF-κB signaling are known to increase cytokines and proteases, which accelerate matrix degradation. Therefore, TLR2 or NF-κB inhibition may both attenuate chronic pain and slow the degenerative progress in vivo.
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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.