A Translational Model for Repeated Episodes of Joint Inflammation: Welfare, Clinical and Synovial Fluid Biomarker Assessment.
Abstract: This study investigates repeated low-dose lipopolysaccharide (LPS) injections in equine joints as a model for recurrent joint inflammation and its impact on animal welfare. Joint inflammation was induced in eight horses by injecting 0.25 ng of LPS three times at two-week intervals. Welfare scores and clinical parameters were recorded at baseline and over 168 h post-injection. Serial synoviocentesis was performed for the analysis of a panel of synovial fluid biomarkers of inflammation and cartilage turnover. Clinical parameters and a final synoviocentesis were also performed eight weeks after the last sampling point to assess the recovery of normal joint homeostasis. Statistical methods were used to compare the magnitude of response to each of the 3 LPS inductions and to compare the baseline and final measurements. Each LPS injection produced consistent clinical and biomarker responses, with minimal changes in welfare scores. General matrix metalloproteinase (MMP) activity and joint circumference showed greater response to the second LPS induction, but response to the third was comparable to the first. Gylcosaminoglycans (GAG) levels showed a significantly decreased response with each induction, while collagen-cleavage neoepitope of type II collagen (C2C) and carboxypropetide of type II collagen epitope (CPII) showed quicker responses to the second and third inductions. All parameters were comparable to baseline values at the final timepoint. In conclusion, a consistent, reliable intra-articular inflammatory response can be achieved with repeated injections of 0.25 ng LPS, with minimal impact on animal welfare, suggesting potential as a refined translational model of recurrent joint inflammation.
Publication Date: 2023-10-12 PubMed ID: 37893914PubMed Central: PMC10603652DOI: 10.3390/ani13203190Google Scholar: Lookup
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- Journal Article
Summary
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The research article is centered on studying repeated inflammation in equine joints caused by low-dose lipopolysaccharide injections. This is done to model recurrent joint inflammation and its effects on the welfare of the animal.
Objectives and Method of the Study
- The main objective of this study was to develop a reusable model for recurrent inflammation in joints. This model would aid in understanding and potentially treating such conditions in equines and other animals.
- The study applied repeated low-dose injections of lipopolysaccharide, also known as LPS, into the joints of eight horses.
- Injections were performed three times with two-week intervals. The horses were then clinically evaluated for any signs of inflammation over a period of 168 hours post-injection.
- Alongside this, synoviocentesis was performed several times. This involved extraction and analysis of synovial fluid for inflammation and cartilage turnover biomarkers. This procedure was also performed eight weeks after the last mapping point to understand how well the joint returned to its normal status.
Findings of the Study
- The research demonstrated that each lipopolysaccharide injection consistently induced inflammation, as indicated by the clinical and biomarker responses. The horses experienced relatively minor changes in their welfare scores, implying that the model has minimal animal welfare impact.
- The response to the second LPS injection was generally greater than the first, particularly in terms of general matrix metalloproteinase (which causes collagen degradation and joint destabilization) activity and joint circumference. However, the third response was found to be similar to the initial one.
- Glycosaminoglycans (components of cartilage that play a crucial role in resisting compression) showed reduced action with each injection. In contrast, the collagen-cleavage neoepitope of type II collagen (which marks collagen degradation) and carboxypropetide of type II collagen epitope (indicating collagen synthesis) manifested quicker reactions to the second and third introductions.
- All parameters including symptoms, joint circumference, biomarker levels, and more showed the equivalent results to the baseline measurements at the final timepoint. This suggests that the horse’s joints returned to normality eight weeks post-testing.
Conclusion
- The research illustrates a successful model for managing recurrent joint inflammation while minimizing impact on animal welfare. Using low-dose LPS injections, the study managed to consistently induce joint inflammation that recovered to baseline values. This indicates this approach has potential as a dependable model for investigating the effects and treatments of recurrent joint inflammation.
Cite This Article
APA
Kearney CM, Korthagen NM, Plomp SGM, Labberté MC, de Grauw JC, van Weeren PR, Brama PAJ.
(2023).
A Translational Model for Repeated Episodes of Joint Inflammation: Welfare, Clinical and Synovial Fluid Biomarker Assessment.
Animals (Basel), 13(20).
https://doi.org/10.3390/ani13203190 Publication
Researcher Affiliations
- UCD School of Veterinary Medicine, University College Dublin, D04 W6F6 Dublin, Ireland.
- Department of Clinical Sciences, Faculty of Veterinary Medicine, Utrecht University, 3584 CM Utrecht, The Netherlands.
- Department of Clinical Sciences, Faculty of Veterinary Medicine, Utrecht University, 3584 CM Utrecht, The Netherlands.
- UCD School of Veterinary Medicine, University College Dublin, D04 W6F6 Dublin, Ireland.
- Department of Clinical Sciences and Services, Royal Veterinary College, University of London, Hatfield AL9 7TA, UK.
- Department of Clinical Sciences, Faculty of Veterinary Medicine, Utrecht University, 3584 CM Utrecht, The Netherlands.
- UCD School of Veterinary Medicine, University College Dublin, D04 W6F6 Dublin, Ireland.
Grant Funding
- Wellcome Trust
Conflict of Interest Statement
The authors declare no conflict of interest.
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