ArticleJOR spine2021
TRPV4 mediates cell damage induced by hyperphysiological compression and regulates COX2/PGE2 in intervertebral discs.
Article in JOR spine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 23 citations in OpenAlex.
- The emerging role of lactate in skeletal homeostasis and disorders: Integrated mechanisms and translational opportunities.Journal of orthopaedic translation · 2026Review
- Mechanotransduction in intervertebral disc degeneration: from compartment-specific sensors to translational frontiers.Frontiers in bioengineering and biotechnology · 2026Review
- Soluble epoxide hydrolase inhibition restores pro-resolving lipid mediators and reduces inflammation in localized provoked vulvodynia.Frontiers in pharmacology · 2026Article
- From mechanotransduction to manual therapy: advances in piezo/TRP channels and lumbar degeneration.Frontiers in physiology · 2026Review
- An overview of mechanical microenvironment and mechanotransduction in intervertebral disc degeneration.Experimental & molecular medicine · 2025Review
- Electric currents in disc health: The role of ion channels in intervertebral disc pathophysiology.Journal of orthopaedic translation · 2025Review
- Review
- The relationship between biomechanical factors and intervertebral disc degeneration: a review.American journal of translational research · 2025Review
- Impact of TRP Channels on Extracellular Matrix Remodeling: Focus on TRPV4 and Collagen.International journal of molecular sciences · 2024Review
- The role of TRPV4 in programmed cell deaths.Molecular biology reports · 2024Review
- Synergetic role of TRPV4 inhibitor and mechanical loading on reducing inflammation.Frontiers in immunology · 2024Article
- Radiographical Survey of Osteochondrodysplasia in Scottish Fold Cats caused by the TRPV4 gene variant.Human genetics · 2021Article
- TRPV4 mediates cell damage induced by hyperphysiological compression and regulates COX2/PGE2 in intervertebral discs.JOR spine · 2021Article
- Intervertebral Disc-on-a-Chip as AdvancedFrontiers in bioengineering and biotechnology · 2021Review
Corrections and comments
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Authors and funding
10 authors at 5 institutions in 5 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundAberrant mechanical loading of the spine causes intervertebral disc (IVD) degeneration and low back pain. Current therapies do not target the mediators of the underlying mechanosensing and mechanotransduction pathways, as these are poorly understood. This study investigated the role of the mechanosensitive transient receptor potential vanilloid 4 (TRPV4) ion channel in dynamic compression of bovine nucleus pulposus (NP) cells in vitro and mouse IVDs in vivo.
methodsDegenerative changes and the expression of the inflammatory mediator cyclooxygenase 2 (COX2) were examined histologically in the IVDs of mouse tails that were dynamically compressed at a short repetitive hyperphysiological regime (vs sham). Bovine NP cells embedded in an agarose-collagen hydrogel were dynamically compressed at a hyperphysiological regime in the presence or absence of the selective TRPV4 antagonist GSK2193874. Lactate dehydrogenase (LDH) and prostaglandin E2 (PGE2) release, as well as phosphorylation of mitogen-activated protein kinases (MAPKs), were analyzed. Degenerative changes and COX2 expression were further evaluated in the IVDs of trpv4-deficient mice (vs wild-type; WT).
resultsDynamic compression caused IVD degeneration in vivo as previously shown but did not affect COX2 expression. Dynamic compression significantly augmented LDH and PGE2 releases in vitro, which were significantly reduced by TRPV4 inhibition. Moreover, TRPV4 inhibition during dynamic compression increased the activation of the extracellular signal-regulated kinases 1/2 (ERK) MAPK pathway by 3.13-fold compared to non-compressed samples. Trpv4-deficient mice displayed mild IVD degeneration and decreased COX2 expression compared to WT mice.
conclusionsTRPV4 therefore regulates COX2/PGE2 and mediates cell damage induced by hyperphysiological dynamic compression, possibly via ERK. Targeted TRPV4 inhibition or knockdown might thus constitute promising therapeutic approaches to treat patients suffering from IVD pathologies caused by aberrant mechanical stress.
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