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Equine veterinary journal2016; 49(1); 107-115; doi: 10.1111/evj.12531

Cytokine, catabolic enzyme and structural matrix gene expression in synovial fluid following intra-articular administration of triamcinolone acetonide in exercised horses.

Abstract: The frequent use of intra-articular triamcinolone acetonide (TA) in performance horses warrants further study of the duration of as well as the beneficial and detrimental effects on gene expression associated with administration. Objective: To assess the effects of intra-articular administration of TA on the expression of selected anti- and proinflammatory and structural matrix genes following its administration into joints of exercised Thoroughbred horses and to correlate these effects with plasma and synovial fluid drug concentrations. Methods: Block design experiment. Methods: Eight exercised horses received a single intra-articular administration of 9 mg of TA. Synovial fluid samples were collected from the treated and contralateral joints prior to and up to 49 days following drug administration. Microarray and quantitative reverse transcription polymerase chain reaction analysis were used to assess changes in expression levels of various inflammatory and structural genes post drug administration. Results: Drug concentrations in plasma and synovial fluid, were no longer quantifiable by 6 and 28 days following drug administration respectively. In total, the expression level of 5490 genes were significantly altered on micro array analysis, following intra-articular TA administration. Of the genes selected for further study by quantitative reverse transcription polymerase chain reaction analysis, significant changes in inflammatory genes (annexin type 1, cyclooxygenase-1 and tumour necrosis factor stimulated gene 6) and structural genes (collagen and aggrecan) were noted. Conclusions: This study supports the use of synovial fluid as a biological matrix for studying the effects of corticosteroids on gene expression. For the majority of genes studied the effects on expression relative to baseline for both inflammatory and matrix genes were prolonged relative to plasma and synovial fluid TA concentrations. Downregulation of collagen gene expression warrants the careful use of TA in horses.
Publication Date: 2016-01-08 PubMed ID: 26518341DOI: 10.1111/evj.12531Google Scholar: Lookup
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  • Journal Article

Summary

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This study investigates the impact of intra-articular administration of triamcinolone acetonide (TA) on the gene expression related to inflammation and structural matrix in the joints of exercised Thoroughbred horses. The effects are tracked alongside corresponding plasma and synovial fluid drug concentrations. The study finds that while drug concentrations disappear within 28 days of administration, their impact on gene expressions endures for much longer.

Objective and Methodology

The study was designed to assess the impact of TA on anti- and proinflammatory genes and structural matrix genes. TA is commonly used in treating performance horses, but its effects, especially long-term ones, have not been thoroughly studied.

  • In this block-design experiment, eight exercised Thoroughbred horses were administered 9 mg of TA intra-articularly and the synovial fluid was sampled. The samples were taken from both treated and contralateral joints before the drug administration and up to 49 days afterwards.
  • The researchers used microarray and quantitative reverse transcription polymerase chain reaction analysis to study the changes in the expression levels of various inflammatory and structural genes after the drug administration.

Results

  • The research found that drug concentrations in plasma and synovial fluids were no longer measurable after 6 and 28 days respectively.
  • However, microarray analysis showed significant changes in the expression level of 5490 genes after the administration of TA. More specifically, considerable changes in inflammatory genes (annexin type 1, cyclooxygenase-1, and tumour necrosis factor stimulated gene 6) and structural genes (collagen and aggrecan) were observed.

Conclusions

  • The study supports the use of synovial fluid as a mechanism for studying the effects of corticosteroids on gene expression. This is mainly due to the prolonged effects on gene expression, both inflammatory and matrix genes, compared to the presence of TA in plasma and synovial fluid.
  • Additionally, the significant downregulation of collagen gene expression suggests careful use of TA in horses as it may lead to potential structural defects in the long run.

Cite This Article

APA
Knych HK, Vidal MA, Chouicha N, Mitchell M, Kass PH. (2016). Cytokine, catabolic enzyme and structural matrix gene expression in synovial fluid following intra-articular administration of triamcinolone acetonide in exercised horses. Equine Vet J, 49(1), 107-115. https://doi.org/10.1111/evj.12531

Publication

ISSN: 2042-3306
NlmUniqueID: 0173320
Country: United States
Language: English
Volume: 49
Issue: 1
Pages: 107-115

Researcher Affiliations

Knych, H K
  • K.L. Maddy Equine Analytical Chemistry Laboratory, School of Veterinary Medicine, University of California, Davis, USA.
  • Department of Veterinary Molecular Biosciences, School of Veterinary Medicine, University of California, Davis, USA.
Vidal, M A
  • Department of Surgery and Radiology, School of Veterinary Medicine, University of California, Davis, USA.
Chouicha, N
  • K.L. Maddy Equine Analytical Chemistry Laboratory, School of Veterinary Medicine, University of California, Davis, USA.
Mitchell, M
  • K.L. Maddy Equine Analytical Chemistry Laboratory, School of Veterinary Medicine, University of California, Davis, USA.
Kass, P H
  • Department of Health and Reproduction, School of Veterinary Medicine, University of California, Davis, USA.

MeSH Terms

  • Animals
  • Anti-Inflammatory Agents / administration & dosage
  • Anti-Inflammatory Agents / pharmacology
  • Biomarkers
  • Cytokines / chemistry
  • Cytokines / genetics
  • Cytokines / metabolism
  • Gene Expression Regulation / drug effects
  • Horses / physiology
  • Injections, Intra-Articular / veterinary
  • Physical Conditioning, Animal
  • Protein Array Analysis / veterinary
  • Synovial Fluid / chemistry
  • Triamcinolone Acetonide / administration & dosage
  • Triamcinolone Acetonide / pharmacology

Citations

This article has been cited 2 times.
  1. Chakrabarti S, Ai M, Henson FMD, Smith ESJ. Peripheral mechanisms of arthritic pain: A proposal to leverage large animals for in vitro studies.. Neurobiol Pain 2020 Aug-Dec;8:100051.
    doi: 10.1016/j.ynpai.2020.100051pubmed: 32817908google scholar: lookup
  2. Castro Martins M, Peffers MJ, Lee K, Rubio-Martinez LM. Effects of stanozolol on normal and IL-1β-stimulated equine chondrocytes in vitro.. BMC Vet Res 2018 Mar 20;14(1):103.
    doi: 10.1186/s12917-018-1426-zpubmed: 29554899google scholar: lookup