Equine osteoarthritis modifies fatty acid signatures in synovial fluid and its extracellular vesicles

Anne-Mari Mustonen; Nina Lehmonen; Tommi Paakkonen; Marja Raekallio; Reijo Käkelä; Tytti Niemelä; Anna Mykkänen; Sanna P Sihvo; Petteri Nieminen

doi:10.1186/s13075-023-02998-9

Equine osteoarthritis modifies fatty acid signatures in synovial fluid and its extracellular vesicles

Arthritis Res Ther. 2023 Mar 9;25(1):39. doi: 10.1186/s13075-023-02998-9.

Authors

Anne-Mari Mustonen^{1

2}, Nina Lehmonen³, Tommi Paakkonen⁴, Marja Raekallio³, Reijo Käkelä^{5

6}, Tytti Niemelä³, Anna Mykkänen³, Sanna P Sihvo^{5

6}, Petteri Nieminen⁴

Affiliations

¹ 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.
² 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.
³ Department of Equine and Small Animal Medicine, Faculty of Veterinary Medicine, University of Helsinki, P.O. Box 57, FI-00014, Helsinki, Finland.
⁴ Institute of Biomedicine, School of Medicine, Faculty of Health Sciences, University of Eastern Finland, P.O. Box 1627, FI-70211, Kuopio, Finland.
⁵ Molecular and Integrative Biosciences Research Programme, Faculty of Biological and Environmental Sciences, University of Helsinki, P.O. Box 65, FI-00014, Helsinki, Finland.
⁶ Helsinki University Lipidomics Unit (HiLIPID), Helsinki Institute of Life Science (HiLIFE) and Biocenter Finland, P.O. Box 65, FI-00014, Helsinki, Finland.

Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

Keywords: Extracellular vesicle; Fatty acid; Horse; Joint disease; Osteoarthritis; Synovial fluid.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Extracellular Vesicles* / metabolism
Extracellular Vesicles* / pathology
Fatty Acids / metabolism
Horses
Humans
Joint Diseases*
Osteoarthritis* / metabolism
Synovial Fluid / metabolism

Substances

Fatty Acids