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Home / Equine Research Bank / Animals (Basel) / Refinement of the Lipopolysaccharide-Induced Synovitis Model...
Animals : an open access journal from MDPI2025; 15(17); 2474; doi: 10.3390/ani15172474

Refinement of the Lipopolysaccharide-Induced Synovitis Model in Equine Middle Carpal Joints.

Abstract: The aim of this study was to refine the lipopolysaccharide (LPS)-induced synovitis model in normal carpal joints of Thoroughbred horses by comparing two low LPS doses. A further aim was to investigate the relationship between the induced synovitis and lameness. The study design consisted of two phases using nine horses with a unilateral crossover design and a within-animal saline control. Synoviocentesis was performed at post-injection hour (PIH) 0, 8, 24, 72 and 168, allowing for synovial fluid cytology and biomarker analysis. Objective gait and thermographic analysis were used to objectively measure clinical effects. The results demonstrate that injection of either a 0.125 ng or 0.25 ng dose of LPS induces a comparable degree of synovitis in terms of TP, WBC, PGE and MMP activity at peak values. Statistically significant changes in baseline lameness values were not detected with the 0.125 ng dose, a novel and valuable finding suggesting a comparable degree of synovitis is achieved without significant lameness. All measured parameters had returned to baseline by PIH 168. In conclusion, the findings of this study confirm that this LPS model produces a consistent and reliable synovitis at 0.25 ng and 0.125 ng doses. The reduction in lameness evident at the 0.125 ng dose offers enhanced animal welfare while delivering measurable synovitis. The authors believe that a further reduction in the LPS dose is possible with continued development of a repeated low-dose/slow-release model to better mimic clinical disease.
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Publication Date: 2025-08-22 PubMed ID: 40941269PubMed Central: PMC12427284DOI: 10.3390/ani15172474Google Scholar: Lookup
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  • Journal Article

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

Overview

  • This study aimed to refine a model of joint inflammation (synovitis) in horse carpal joints by testing two low doses of lipopolysaccharide (LPS) and to explore how the inflammation relates to lameness in horses.
  • The research found that both doses caused similar levels of joint inflammation, but the lower dose induced less lameness, suggesting a gentler and more welfare-friendly model for studying synovitis.

Background and Aim

  • Synovitis is an inflammation of the synovial membrane in joints, often used as a model for studying joint disease in horses.
  • Lipopolysaccharide (LPS) is a bacterial endotoxin used to induce synovitis experimentally.
  • The study aimed to refine this model by:
    • Comparing two low doses of LPS (0.125 ng and 0.25 ng) in Thoroughbred horses’ middle carpal joints.
    • Investigating the relationship between the induced synovitis and the clinical sign of lameness.

Study Design and Methods

  • Subjects & Design:
    • Nine Thoroughbred horses were used.
    • A unilateral crossover design was applied, meaning each horse served as its own control with one joint injected with saline and the other with LPS at different times.
  • Interventions:
    • Two different low doses of LPS were injected into middle carpal joints: 0.125 ng and 0.25 ng.
  • Data Collection:
    • Synoviocentesis (joint fluid sampling) was performed at baseline (0 hours) and then at 8, 24, 72, and 168 hours post-injection (PIH).
    • Synovial fluid was analyzed for cytology and biomarkers:
      • TP (total protein)
      • WBC (white blood cell count)
      • PGE (prostaglandin E)
      • MMP (matrix metalloproteinase) activity
    • Objective assessments of lameness using gait analysis and thermography were performed to measure clinical effects.

Key Findings

  • Both doses (0.125 ng and 0.25 ng) induced similar peak levels of synovitis based on:
    • Total protein in joint fluid
    • White blood cell counts
    • Prostaglandin E levels
    • Matrix metalloproteinase activity
  • Lameness:
    • The higher dose (0.25 ng) produced changes in lameness.
    • The lower dose (0.125 ng) did not produce statistically significant increases in lameness compared to baseline, indicating reduced discomfort for the animals.
  • All markers of inflammation and clinical signs returned to baseline by 168 hours (7 days) after injection.

Conclusions and Implications

  • The study confirms that low-dose LPS is effective for producing reliable and consistent synovitis in equine joints suitable for experimental studies.
  • The 0.125 ng LPS dose is advantageous as it causes a measurable inflammatory response without significant lameness, improving animal welfare during experiments.
  • The authors suggest that further dose reduction or the development of slow-release LPS models could better simulate chronic joint disease, enabling ongoing research with minimal animal discomfort.
  • Overall, this refined synovitis model strikes a balance between research needs and horse welfare.

Cite This Article

APA
Duggan MJS, Kearney C, Baltrimaite M, Labberté MC, Gibney R, Brama PAJ. (2025). Refinement of the Lipopolysaccharide-Induced Synovitis Model in Equine Middle Carpal Joints. Animals (Basel), 15(17), 2474. https://doi.org/10.3390/ani15172474

Publication

Animals : an open access journal from MDPI
ISSN: 2076-2615
NlmUniqueID: 101635614
Country: Switzerland
Language: English
Volume: 15
Issue: 17
PII: 2474

Researcher Affiliations

Duggan, Michael J S
  • School of Veterinary Medicine, UCD Veterinary Hospital, University College Dublin, D04 W6F6 Dublin, Ireland.
Kearney, Clodagh
  • School of Veterinary Medicine, UCD Veterinary Hospital, University College Dublin, D04 W6F6 Dublin, Ireland.
Baltrimaite, Milda
  • School of Veterinary Medicine, UCD Veterinary Hospital, University College Dublin, D04 W6F6 Dublin, Ireland.
Labberté, Margot C
  • School of Veterinary Medicine, UCD Veterinary Hospital, University College Dublin, D04 W6F6 Dublin, Ireland.
Gibney, Rory
  • Trinity Centre for Bioengineering, Trinity Biomedical Sciences Institute, Trinity College Dublin, D02 R590 Dublin, Ireland.
Brama, Pieter A J
  • School of Veterinary Medicine, UCD Veterinary Hospital, University College Dublin, D04 W6F6 Dublin, Ireland.

Grant Funding

  • SF1592 / UCD Seed Funding Grant
  • R21299 / UCD In House Schemes Grant: Optimisation Of Translational Large Animal Models
  • TRU-Brama / UCD Lyons Translational Research Unit

Conflict of Interest Statement

The authors declare no conflict of interest.

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Citations

This article has been cited 1 times.
  1. Korac L, St George L, MacNicol J, McCrae P, Jung L, Golestani N, Karrow N, Cánovas A, Pearson W. Functional and biochemical inflammatory responses to low-dose intra-articular recombinant equine IL-1β: a pilot study. Front Vet Sci 2025;12:1746738.
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