Evaluation of the inflammatory response in experimentally induced synovitis in the horse: a comparison of recombinant equine interleukin 1 beta and lipopolysaccharide.
Abstract: To compare two transient models of synovitis-osteoarthritis (OA) in horses by characterizing biological changes in synovial fluid and joint tissue. Methods: Twelve skeletally mature mares were utilized in a block design. Synovitis was induced by an intra-articular injection of 100 ng recombinant equine interleukin 1 beta (reIL-1β) or 0.5 ng lipopolysaccharide (LPS) into a middle carpal joint in 1 ml volumes. One ml of saline was injected into the contra-lateral control joint. Lameness evaluations were conducted through post-injection hour (PIH) 8 (at which time arthroscopic removal of synovium and articular biopsies was done), and at PIH 240. Arthrocentesis collection of synovial fluid occurred between PIH 0 and 48. An arthroscopic examination at PIH 8 included synovium and articular cartilage biopsies for gene expression analysis. Results: Synovial fluid analysis indicated that single injections of reIL-1β or LPS increased synovial white blood cell (WBC), neutrophil count, total protein, prostaglandin E(2) (PGE(2)) concentrations and general matrix metalloproteinase (MMP) activity relative to control joints through PIH 8. Injections of either reIL-1β or LPS increased mRNA expression for MMP-1 and a disintegrin and metalloprotease with thrombospondin motifs (ADAMTS)-4 in synovium and for MMP-1, ADAMTS-4, ADAMTS-5 in articular cartilage collected at PIH 8 compared to saline injections. Conclusions: Injections of reIL-1β into equine carpal joints resulted in a transient inflammatory response that was similar in severity to the LPS injection, causing increased expression of certain deleterious mediators in joint tissues at 8 h. Given that IL-1β is a known critical mediator of traumatic arthritis and OA, this humane and temporary model may be useful in evaluating therapeutics that act against early stages of joint disease.
Copyright © 2012 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.
Publication Date: 2012-08-21 PubMed ID: 22917743DOI: 10.1016/j.joca.2012.08.008Google Scholar: Lookup
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- Comparative Study
- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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This research investigates two models of arthritis in horses, both induced by injection into the joints. The results showed that both models produced comparable inflammatory responses, indicating they can be useful for studying arthritis treatments.
Introduction and Methodology
- The study aimed to compare two transient synovitis, a condition often leading to osteoarthritis (OA) in horses. In other words, it sought to compare two methods of temporarily inducing joint inflammation that is similar to the conditions seen in horses with arthritis.
- Utilising twelve grown-up mares, the researchers created controlled conditions to induce a type of inflammation that resembles arthritis. This was done by injecting interleukin 1 beta or lipopolysaccharide into a joint in the horse’s leg.
- A control group was also set up, where the opposite joint received a saline injection.
- The impact and changes were assessed at various time intervals post-injection, both through lameness evaluations and drawing out synovial fluid for analysis. Furthermore, the researchers also took biopsies of synovium and articular cartilage for gene expression analysis.
Results
- The synovial fluid analysis showed increased markers of inflammation after the injections of interleukin 1 beta or lipopolysaccharide. These included increased synovial white blood cell and neutrophil count, total protein, prostaglandin E(2) concentrations, and general matrix metalloproteinase (MMP) activity, compared to control joints.
- Increased mRNA expression for MMP-1 and ADAMTS-4 was found in the synovium, and for MMP-1, ADAMTS-4, and ADAMTS-5 in the articular cartilage, compared to samples taken after saline injections. These results suggest that the injections induced inflammation and began to break down joint tissues, similar to the process seen in arthritis.
Conclusions
- The induced inflammation models served their purpose by simulating arthritic conditions in a controlled, transient manner.
- Both types of injections led to similar inflammatory responses, indicating that these models could be fair equivalents for such research purposes.
- Given that interleukin 1 beta is known to play a critical role in arthritis and OA, these models can aid in the understanding of these conditions and the evaluation of possible therapeutic interventions.
Cite This Article
APA
Ross TN, Kisiday JD, Hess T, McIlwraith CW.
(2012).
Evaluation of the inflammatory response in experimentally induced synovitis in the horse: a comparison of recombinant equine interleukin 1 beta and lipopolysaccharide.
Osteoarthritis Cartilage, 20(12), 1583-1590.
https://doi.org/10.1016/j.joca.2012.08.008 Publication
Researcher Affiliations
- Department of Clinical Sciences and Gail Holmes Equine Orthopaedic Research Center, Colorado State University, Fort Collins, CO 80523, USA.
MeSH Terms
- ADAM Proteins / biosynthesis
- ADAM Proteins / genetics
- ADAMTS4 Protein
- Animals
- Arthroscopy
- Biopsy
- Cartilage, Articular / metabolism
- Cartilage, Articular / pathology
- Gene Expression Regulation
- Injections, Intra-Articular
- Interleukin-1beta / administration & dosage
- Interleukin-1beta / toxicity
- Lipopolysaccharides / administration & dosage
- Lipopolysaccharides / toxicity
- Male
- Matrix Metalloproteinase 1 / biosynthesis
- Matrix Metalloproteinase 1 / genetics
- Procollagen N-Endopeptidase / biosynthesis
- Procollagen N-Endopeptidase / genetics
- RNA / genetics
- Recombinant Proteins
- Reverse Transcriptase Polymerase Chain Reaction
- Severity of Illness Index
- Synovial Fluid / drug effects
- Synovial Fluid / metabolism
- Synovitis / chemically induced
- Synovitis / metabolism
- Synovitis / pathology
Citations
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