Equine osteoarthritis modifies fatty acid signatures in synovial fluid and its extracellular vesicles.
Abstract: Individual fatty acids (FAs) and their derivatives (lipid mediators) with pro-inflammatory or dual anti-inflammatory and pro-resolving properties have potential to influence the health of joint tissues. Osteoarthritis (OA) is an age-associated chronic joint disease that can be featured with altered FA composition in the synovial fluid (SF) of human patients. The counts and cargo of extracellular vesicles (EVs), membrane-bound particles released by synovial joint cells and transporting bioactive lipids, can also be modified by OA. The detailed FA signatures of SF and its EVs have remained unexplored in the horse - a well-recognized veterinary model for OA research. The aim of the present study was to compare the FA profiles in equine SF and its ultracentrifuged EV fraction between control, contralateral, and OA metacarpophalangeal joints (n = 8/group). The FA profiles of total lipids were determined by gas chromatography and the data compared with univariate and multivariate analyses. The data revealed distinct FA profiles in SF and its EV-enriched pellet that were modified by naturally occurring equine OA. Regarding SFs, linoleic acid (generalized linear model, p = 0.0006), myristic acid (p = 0.003), palmitoleic acid (p < 0.0005), and n-3/n-6 polyunsaturated FA ratio (p < 0.0005) were among the important variables that separated OA from control samples. In EV-enriched pellets, saturated FAs palmitic acid (p = 0.020), stearic acid (p = 0.002), and behenic acid (p = 0.003) indicated OA. The observed FA modifications are potentially detrimental and could contribute to inflammatory processes and cartilage degradation in OA. Equine OA joints can be distinguished from normal joints based on their FA signatures in SF and its EV-enriched pellet. Clarifying the roles of SF and EV FA compositions in the pathogenesis of OA and their potential as joint disease biomarkers and therapeutic targets warrants future studies.
© 2023. The Author(s).
Publication Date: 2023-03-09 PubMed ID: 36895037PubMed Central: PMC9996872DOI: 10.1186/s13075-023-02998-9Google Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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This research investigates how osteoarthritis (OA) in horses changes the fatty acid (FA) profiles in synovial fluid (SF) and its extracellular vesicles (EVs). The study revealed that these FA compositions differ between healthy and OA joints, potentially contributing to inflammation and cartilage degradation in OA.
Objective of the Research
- The researchers aimed to examine the changes in FA profiles in equine SF and its ultracentrifuged EV fraction among healthy, contralateral, and OA metacarpophalangeal joints. The horse was chosen as a subject due to its status as a recognized veterinary model for OA research.
Methods Used in the Study
- The FA profiles of total lipids were determined using gas chromatography, a technique that allows the separation and analysis of lipids.
- The data was compared using both univariate and multivariate analyses.
Key Findings of the Research
- The data revealed distinct FA profiles in SF and its EV-enriched pellets that were modified by naturally occurring equine OA.
- In the SF, a high concentration of linoleic acid, myristic acid, palmitoleic acid, and a lower n-3/n-6 polyunsaturated FA ratio were associated with OA.
- In EV-enriched pellets, higher concentrations of saturated FAs such as palmitic acid, stearic acid, and behenic acid indicated OA.
Implications and Future Directions
- The altered FA compositions could potentially worsen OA by driving inflammatory processes and supporting cartilage degradation.
- The distinct FA profiles found in OA joints compared to healthy ones suggests that these FAs could serve as potential biomarkers for OA, helping in early detection and treatment of the disease.
- Further studies are warranted to clarify the roles of SF and EV FA compositions in the pathogenesis of OA and their potential as therapeutic targets.
Cite This Article
APA
Mustonen AM, Lehmonen N, Paakkonen T, Raekallio M, Käkelä R, Niemelä T, Mykkänen A, Sihvo SP, Nieminen P.
(2023).
Equine osteoarthritis modifies fatty acid signatures in synovial fluid and its extracellular vesicles.
Arthritis Res Ther, 25(1), 39.
https://doi.org/10.1186/s13075-023-02998-9 Publication
Researcher Affiliations
- Institute of Biomedicine, School of Medicine, Faculty of Health Sciences, University of Eastern Finland, P.O. Box 1627, FI-70211, Kuopio, Finland. anne-mari.mustonen@uef.fi.
- Department of Environmental and Biological Sciences, Faculty of Science, Forestry and Technology, University of Eastern Finland, P.O. Box 111, FI-80101, Joensuu, Finland. anne-mari.mustonen@uef.fi.
- Department of Equine and Small Animal Medicine, Faculty of Veterinary Medicine, University of Helsinki, P.O. Box 57, FI-00014, Helsinki, Finland.
- Institute of Biomedicine, School of Medicine, Faculty of Health Sciences, University of Eastern Finland, P.O. Box 1627, FI-70211, Kuopio, Finland.
- Department of Equine and Small Animal Medicine, Faculty of Veterinary Medicine, University of Helsinki, P.O. Box 57, FI-00014, Helsinki, Finland.
- Molecular and Integrative Biosciences Research Programme, Faculty of Biological and Environmental Sciences, University of Helsinki, P.O. Box 65, FI-00014, Helsinki, Finland.
- Helsinki University Lipidomics Unit (HiLIPID), Helsinki Institute of Life Science (HiLIFE) and Biocenter Finland, P.O. Box 65, FI-00014, Helsinki, Finland.
- Department of Equine and Small Animal Medicine, Faculty of Veterinary Medicine, University of Helsinki, P.O. Box 57, FI-00014, Helsinki, Finland.
- Department of Equine and Small Animal Medicine, Faculty of Veterinary Medicine, University of Helsinki, P.O. Box 57, FI-00014, Helsinki, Finland.
- Molecular and Integrative Biosciences Research Programme, Faculty of Biological and Environmental Sciences, University of Helsinki, P.O. Box 65, FI-00014, Helsinki, Finland.
- Helsinki University Lipidomics Unit (HiLIPID), Helsinki Institute of Life Science (HiLIFE) and Biocenter Finland, P.O. Box 65, FI-00014, Helsinki, Finland.
- Institute of Biomedicine, School of Medicine, Faculty of Health Sciences, University of Eastern Finland, P.O. Box 1627, FI-70211, Kuopio, Finland.
MeSH Terms
- Humans
- Horses
- Animals
- Synovial Fluid / metabolism
- Osteoarthritis / metabolism
- Joint Diseases
- Fatty Acids / metabolism
- Extracellular Vesicles / metabolism
- Extracellular Vesicles / pathology
Conflict of Interest Statement
The authors declare no competing interests.
References
This article includes 74 references
Citations
This article has been cited 9 times.- Wang T, Ng CY, Ng BZJ, Toh WS, Hui JHP. Multi-omics analysis of small extracellular vesicles in osteoarthritis: bridging the gap between molecular insights and clinical applications. Burns Trauma 2025;13:tkaf023.
- González-Rodríguez A, De Toro FJ, Jorge-Mora A, Fernandez-Pernas P, Rivadulla CP, Fraga M, Fafián-Labora JA, Arufe MC. Targeting osteoarthritis with small extracellular vesicle therapy: potential and perspectives. Front Bioeng Biotechnol 2025;13:1570526.
- Liu X, Zheng Y, Li H, Ma Y, Cao R, Zheng Z, Tian Y, Du L, Zhang J, Zhang C, Gao J. The role of metabolites in the progression of osteoarthritis: Mechanisms and advances in therapy. J Orthop Translat 2025 Jan;50:56-70.
- Varela L, van de Lest CHA, van Weeren PR, Wauben MHM. Synovial fluid extracellular vesicles as arthritis biomarkers: the added value of lipid-profiling and integrated omics. Extracell Vesicles Circ Nucl Acids 2024;5(2):276-296.
- Yang W, Xiao W, Liu H. Genetically predicted circulating linoleic acid levels and risk of osteoarthritis: a two-sample mendelian randomization study. BMC Musculoskelet Disord 2024 Nov 13;25(1):903.
- Connard SS, Gaesser AM, Clarke EJ, Linardi RL, Even KM, Engiles JB, Koch DW, Peffers MJ, Ortved KF. Plasma and synovial fluid extracellular vesicles display altered microRNA profiles in horses with naturally occurring post-traumatic osteoarthritis: an exploratory study. J Am Vet Med Assoc 2024 Jun 1;262(S1):S83-S96.
- Deng C, Presle N, Pizard A, Guillaume C, Bianchi A, Kempf H. Beneficial Impact of Eicosapentaenoic Acid on the Adverse Effects Induced by Palmitate and Hyperglycemia on Healthy Rat Chondrocyte. Int J Mol Sci 2024 Feb 2;25(3).
- Anderson JR, Johnson E, Jenkins R, Jacobsen S, Green D, Walters M, Bundgaard L, Hausmans BAC, van den Akker G, Welting TJM, Chabronova A, Kharaz YA, Clarke EJ, James V, Peffers MJ. Multi-Omic Temporal Landscape of Plasma and Synovial Fluid-Derived Extracellular Vesicles Using an Experimental Model of Equine Osteoarthritis. Int J Mol Sci 2023 Oct 4;24(19).
- Mustonen AM, Nieminen P. Dihomo-γ-Linolenic Acid (20:3n-6)-Metabolism, Derivatives, and Potential Significance in Chronic Inflammation. Int J Mol Sci 2023 Jan 20;24(3).
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