mRNA expression of genes involved in inflammation and haemostasis in equine fibroblast-like synoviocytes following exposure to lipopolysaccharide, fibrinogen and thrombin.
Authors: Andreassen Stine Mandrup, Berg Lise C, Nielsen Søren Saxmose, Kristensen Annemarie T, Jacobsen Stine
Journal: BMC veterinary research
Summary
# Editorial Summary Haemostatic dysfunction and inflammation frequently co-occur in equine joint disease, yet the molecular mechanisms linking these pathways remain poorly characterised in horses. Researchers cultured fibroblast-like synoviocytes isolated from the metacarpophalangeal joints of six horses and exposed them to lipopolysaccharide (LPS—a bacterial endotoxin model), fibrinogen, and thrombin at physiologically relevant concentrations, harvesting samples at 6, 24, and 48 hours to measure mRNA expression of eight key inflammatory and haemostatic mediators using quantitative PCR. All three stimuli triggered significant upregulation of inflammatory cytokines (serum amyloid A, interleukin-6, and monocyte chemotactic protein-1) and haemostatic factors (tissue factor, plasminogen activator inhibitor-1, and urokinase plasminogen activator), with responses varying in magnitude and timing depending on the trigger, whilst protease-activated receptor-1 expression increased across all treatment groups. These findings suggest that joint trauma causing localised fibrinogen deposition and thrombin generation may amplify the synovial inflammatory cascade through direct activation of resident synovial cells, implicating haemostatic perturbation as a potential therapeutic target in managing equine joint pathology—particularly relevant for practitioners managing acute joint injuries where both inflammation control and restoration of normal clotting equilibrium could prove clinically significant.
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Practical Takeaways
- •Understanding the link between coagulation activation and joint inflammation may inform future therapeutic targets for managing joint disease in horses
- •Anti-inflammatory and anticoagulant strategies may have complementary roles in treating acute synovitis, though clinical validation is needed
- •The temporal expression patterns suggest early intervention after joint injury may be critical to prevent cascade amplification of inflammation
Key Findings
- •LPS, fibrinogen, and thrombin all induced upregulation of inflammatory markers (SAA, IL-6, MCP-1) in equine fibroblast-like synoviocytes with peak expression at 6-24 hours
- •Thrombin and fibrinogen activated haemostatic pathways, significantly increasing TF and PAI-1 expression
- •PAR-1 expression was upregulated by thrombin and fibrinogen, suggesting protease-activated receptor signaling in synovial inflammation
- •mRNA expression patterns indicate crosstalk between haemostatic and inflammatory pathways in equine joint disease pathogenesis