ArticleCells2020
TRPV4 Inhibition and CRISPR-Cas9 Knockout Reduce Inflammation Induced by Hyperphysiological Stretching in Human Annulus Fibrosus Cells.
Article in Cells, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers, 1 of them a synthesis that pooled it.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
30 citing papers in PubMed, 1 synthesis or guideline pooled it, 38 citations in OpenAlex.
- Mechanobiology of the Human Intervertebral Disc: Systematic Review of the Literature and Future Perspectives.International journal of molecular sciences · 2023Pooled it
- Stem cell therapy for degenerative disc disease: A systematic review of preclinical evidence, clinical translation, and future directions.North American Spine Society journal · 2026Review
- Mechanotransduction in intervertebral disc degeneration: from compartment-specific sensors to translational frontiers.Frontiers in bioengineering and biotechnology · 2026Review
- From mechanotransduction to manual therapy: advances in piezo/TRP channels and lumbar degeneration.Frontiers in physiology · 2026Review
- Article
- Understanding the Microenvironment of Intervertebral Disc Degeneration: A Comprehensive Review of Pathophysiological Insights and Therapeutic Implications.International journal of molecular sciences · 2025Review
- Electric currents in disc health: The role of ion channels in intervertebral disc pathophysiology.Journal of orthopaedic translation · 2025Review
- Review
- Exploring the Causes of Intervertebral Disc Annulus Fibrosus Impairment.Cellular and molecular bioengineering · 2025Review
- Article
- CRISPR-dCas9 Activation of TSG-6 in MSCs Modulates the Cargo of MSC-Derived Extracellular Vesicles and Attenuates Inflammatory Responses in Human Intervertebral Disc Cells In Vitro.Cellular and molecular bioengineering · 2025Article
- Harnessing CRISPR potential for intervertebral disc regeneration strategies.Frontiers in bioengineering and biotechnology · 2025Review
- A Bibliometric Study of Interleukin Cytokines in the Treatment of Intervertebral Disc Degeneration.Drug design, development and therapy · 2025Article
- The relationship between biomechanical factors and intervertebral disc degeneration: a review.American journal of translational research · 2025Review
- Current Therapeutic Strategies of Intervertebral Disc Regenerative Medicine.Molecular diagnosis & therapy · 2024Review
- The role of miR-155-5p in inflammation and mechanical loading during intervertebral disc degeneration.Cell communication and signaling : CCS · 2024Article
- TRPV4 differentially controls inflammatory cytokine networks during static and dynamic compression of the intervertebral disc.JOR spine · 2023Article
- High-Tech Methods of Cytokine Imbalance Correction in Intervertebral Disc Degeneration.International journal of molecular sciences · 2023Review
- Review
- Tuning immunity through tissue mechanotransduction.Nature reviews. Immunology · 2023Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 6 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mechanical loading and inflammation interact to cause degenerative disc disease and low back pain (LBP). However, the underlying mechanosensing and mechanotransductive pathways are poorly understood. This results in untargeted pharmacological treatments that do not take the mechanical aspect of LBP into account. We investigated the role of the mechanosensitive ion channel TRPV4 in stretch-induced inflammation in human annulus fibrosus (AF) cells. The cells were cyclically stretched to 20% hyperphysiological strain. TRPV4 was either inhibited with the selective TRPV4 antagonist GSK2193874 or knocked out (KO) via CRISPR-Cas9 gene editing. The gene expression, inflammatory mediator release and MAPK pathway activation were analyzed. Hyperphysiological cyclic stretching significantly increased the IL6, IL8, and COX2 mRNA, PGE2 release, and activated p38 MAPK. The TRPV4 pharmacological inhibition significantly attenuated these effects. TRPV4 KO further prevented the stretch-induced upregulation of IL8 mRNA and reduced IL6 and IL8 release, thus supporting the inhibition data. We provide novel evidence that TRPV4 transduces hyperphysiological mechanical signals into inflammatory responses in human AF cells, possibly via p38. Additionally, we show for the first time the successful gene editing of human AF cells via CRISPR-Cas9. The pharmacological inhibition or CRISPR-based targeting of TRPV4 may constitute a potential therapeutic strategy to tackle discogenic LBP in patients with AF injury.
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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.