Effect of circadian rhythm, age, training and acute lameness on serum concentrations of cartilage oligomeric matrix protein (COMP) neo-epitope in horses.
Abstract: Molecular serum markers that can identify early reversible osteoarthritis (OA) in horses are lacking. Objective: We studied serum concentrations of a novel cartilage oligomeric matrix protein (COMP) neo-epitope in horses subjected to short-term exercise and with acute lameness. The effects of circadian rhythm and age were also evaluated. Methods: Longitudinal studies in healthy horses and cross-sectional comparison of lame and non-lame horses. Methods: Sera were collected from five horses before and after short-term interval exercise and during full-day box rest. Sera from 32 acutely lame horses were used to evaluate age-related effects. Independent samples from control horses (n = 41) and horses with acute lameness (n = 71) were included. COMP neo-epitope concentrations were analysed using custom-developed inhibition ELISAs validated for equine serum. The presence of COMP neo-epitope was delineated in healthy and osteoarthritic articular cartilage with immunohistochemistry. Results: COMP neo-epitope concentrations decreased after speed training but returned to baseline levels post-exercise. No correlations between age and serum COMP neo-epitope concentrations were found (r = 0.0013). The mean (±s.d.) serum concentration of COMP neo-epitope in independent samples from non-lame horses was 0.84 ± 0.38 μg/mL, and for lame horses was 5.24 ± 1.83 μg/mL (P<0.001). Antibodies against COMP neo-epitope did not stain normal articular cartilage, but intracytoplasmic staining was found in superficial chondrocytes of mild OA cartilage and in the extracellular matrix of moderately osteoarthritic cartilage. Conclusions: ELISA was based on polyclonal antisera rather than a monoclonal antibody. There is a sex and breed bias within the groups of horses, also it could have been of value to include horses with septic arthritis and tendonitis and investigated joint differences. Conclusions: This COMP neo-epitope can be measured in sera, and results indicate that it could be a biomarker for pathologic fragmentation of cartilage in connection with acute joint lameness.
© 2019 The Authors. Equine Veterinary Journal published by John Wiley & Sons Ltd on behalf of EVJ Ltd.
Publication Date: 2019-03-06 PubMed ID: 30739342PubMed Central: PMC6767518DOI: 10.1111/evj.13082Google Scholar: Lookup
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Summary
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The research focuses on determining serum concentrations of a new biomarker, cartilage oligomeric matrix protein (COMP) Neo-epitope, in horses under different conditions aimed at discovering early signs of reversible osteoarthritis (OA). The factors considered include circadian rhythm, age, physical training, and acute lameness. Results indicated the potential of this biomarker in identifying cartilage fragmentation associated with acute joint lameness, which signifies early OA.
Objective and Methods Used
- This research studies the serum concentrations of a new cartilage oligomeric matrix protein (COMP) neo-epitope in horses. The main objective was to identify early reversible osteoarthritis (OA), a condition currently lacking molecular serum markers for early identification.
- Key factors such as circadian rhythm, age, physical training, and acute lameness were considered. The study involved a blend of longitudinal studies in fit horses and cross-sectional comparisons of lame and non-lame horses.
Procedure and Samples
- Samples were collected from five horses before and after short-term exercise and during full-day box rest. Additional samples from 32 lame horses were evaluated for age-related effects.
- The study also included independent samples from control horses (n = 41) and from horses with acute lameness (n = 71).
- COMP neo-epitope concentrations in the collected samples were analyzed using custom-developed inhibition ELISAs, a method validated for equine serum.
- The presence of COMP neo-epitope was further examined in healthy and osteoarthritic articular cartilage using immunohistochemistry.
Results
- The COMP neo-epitope concentrations were found to reduce following speed training but returned back to their baseline levels post-exercise.
- There were no significant correlations between the age of the horses and serum COMP neo-epitope concentration (r = 0.0013), suggesting that age is not a significant factor in COMP neo-epitope levels.
- The mean serum concentration of COMP neo-epitope in non-lame horses was significantly lower than that in lame horses, indicating a potential association between raised COMP neo-epitope levels and lameness.
- Using immunohistochemistry, the antibodies against COMP neo-epitope were not seen in normal articular cartilage but were found in the superficial chondrocytes of mildly affected OA cartilage and in the extracellular matrix of moderately osteoarthritic cartilage.
Conclusion
- The study confirms that COMP neo-epitope can be measured in sera, indicating its potential as a biomarker for cartilage fragmentation related to acute joint lameness in horses.
- The ELISA technique employed in this study was based on polyclonal antisera rather than monoclonal antibodies. The study also acknowledges potential bias due to the sex and breed of horses used, suggesting that future research should address these factors.
Cite This Article
APA
Ekman S, Lindahl A, Rüetschi U, Jansson A, Björkman K, Abrahamsson-Aurell K, Björnsdóttir S, Löfgren M, Hultén LM, Skiöldebrand E.
(2019).
Effect of circadian rhythm, age, training and acute lameness on serum concentrations of cartilage oligomeric matrix protein (COMP) neo-epitope in horses.
Equine Vet J, 51(5), 674-680.
https://doi.org/10.1111/evj.13082 Publication
Researcher Affiliations
- Department of Biomedical Sciences and Veterinary Public Health, Swedish University of Agricultural Sciences, Uppsala, Sweden.
- Department of Clinical Chemistry and Transfusion Medicine, Institute of Biomedicine, Sahlgrenska University Hospital, Gothenburg University, Gothenburg, Sweden.
- Department of Clinical Chemistry and Transfusion Medicine, Institute of Biomedicine, Sahlgrenska University Hospital, Gothenburg University, Gothenburg, Sweden.
- Department of Anatomy, Physiology and Biochemistry, Swedish University of Agricultural Sciences, Uppsala, Sweden.
- Department of Biomedical Sciences and Veterinary Public Health, Swedish University of Agricultural Sciences, Uppsala, Sweden.
- Halland Animal Hospital, Kungsbacka Horse Clinic, Kungsbacka, Sweden.
- Agricultural University of Iceland, Hvanneyri, Borgarnes, Saudarkrokur, Iceland.
- Department of Biomedical Sciences and Veterinary Public Health, Swedish University of Agricultural Sciences, Uppsala, Sweden.
- Department of Molecular and Clinical Medicine, Wallenberg Laboratory, Institute of Medicine, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
- Department of Biomedical Sciences and Veterinary Public Health, Swedish University of Agricultural Sciences, Uppsala, Sweden.
- Department of Clinical Chemistry and Transfusion Medicine, Institute of Biomedicine, Sahlgrenska University Hospital, Gothenburg University, Gothenburg, Sweden.
MeSH Terms
- Aging
- Animals
- Biomarkers
- Cartilage Oligomeric Matrix Protein / blood
- Cartilage Oligomeric Matrix Protein / genetics
- Cartilage Oligomeric Matrix Protein / metabolism
- Circadian Rhythm
- Epitopes / genetics
- Epitopes / metabolism
- Female
- Horse Diseases / blood
- Horse Diseases / diagnosis
- Horse Diseases / metabolism
- Horses
- Lameness, Animal
- Longitudinal Studies
- Male
- Physical Conditioning, Animal
Grant Funding
- ALF GBG-716171 / Western Region Research
- H0947014 / Swedish-Norwegian Foundation for Equine Research
- VR 2015-02959 / Swedish Research Council
- FORMAS 221-2013-317 / Swedish Research Council for Environment, Agricultural Sciences and Spatial Planning
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Citations
This article has been cited 4 times.- Skiöldebrand E, Adepu S, Lützelschwab C, Nyström S, Lindahl A, Abrahamsson-Aurell K, Hansson E. A randomized, triple-blinded controlled clinical study with a novel disease-modifying drug combination in equine lameness-associated osteoarthritis. Osteoarthr Cartil Open 2023 Sep;5(3):100381.
- Sandstedt J, Vargmar K, Björkman K, Ruetschi U, Bergström G, Hultén LM, Skiöldebrand E. COMP (Cartilage Oligomeric Matrix Protein) Neoepitope: A Novel Biomarker to Identify Symptomatic Carotid Stenosis. Arterioscler Thromb Vasc Biol 2021 Mar;41(3):1218-1228.
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