Clarke, Emily, Varela, Laura, Jenkins, Rosalind E, Lozano-Andrés, Estefanía, Cywińska, Anna, Przewozny, Maciej, van Weeren, P René, van de Lest, Chris HA 
ORCID: 0000-0003-2143-2825, Peffers, Mandy ORCID: 0000-0001-6979-0440 and Wauben, Marca HM ORCID: 0000-0003-0360-0311
(2024)
Proteome and phospholipidome interrelationship of synovial fluid-derived extracellular vesicles in equine osteoarthritis: An exploratory 'multi-omics' study to identify composite biomarkers.
Biochemistry and biophysics reports, 37.
101635-.
Abstract
Osteoarthritis causes progressive joint deterioration, severe morbidity, and reduced mobility in both humans and horses. Currently, osteoarthritis is diagnosed at late stages through clinical examination and radiographic imaging, hence it is challenging to address and provide timely therapeutic interventions to slow disease progression or ameliorate symptoms. Extracellular vesicles are cell-derived vesicles that play a key role in cell-to-cell communication and are potential sources for specific composite biomarker panel discovery. We here used a multi-omics strategy combining proteomics and phospholipidomics in an integral approach to identify composite biomarkers associated to purified extracellular vesicles from synovial fluid of healthy, mildly and severely osteoarthritic equine joints. Although the number of extracellular vesicles was unaffected by osteoarthritis, proteome profiling of extracellular vesicles by mass spectrometry identified 40 differentially expressed proteins (non-adjusted p < 0.05) in osteoarthritic joints associated with 7 significant canonical pathways in osteoarthritis. Moreover, pathway analysis unveiled changes in disease and molecular functions during osteoarthritis development. Phospholipidome profiling by mass spectrometry showed a relative increase in sphingomyelin and a decrease in phosphatidylcholine, phosphatidylinositol, and phosphatidylserine in extracellular vesicles derived from osteoarthritic joints compared to healthy joints. Unsupervised data integration revealed positive correlations between the proteome and the phospholipidome. Comprehensive analysis showed that some phospholipids and their related proteins increased as the severity of osteoarthritis progressed, while others decreased or remained stable. Altogether our data show interrelationships between synovial fluid extracellular vesicle-associated phospholipids and proteins responding to osteoarthritis pathology and which could be explored as potential composite diagnostic biomarkers of disease.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | Biomarker, Equine, Extracellular vesicles, Lipidomics, Osteoarthritis, Proteomics, Synovial fluid |
| Divisions: | Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Life Courses and Medical Sciences Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology |
| Depositing User: | Symplectic Admin |
| Date Deposited: | 20 Feb 2024 11:24 |
| Last Modified: | 01 Mar 2024 17:11 |
| DOI: | 10.1016/j.bbrep.2023.101635 |
| Open Access URL: | https://doi.org/10.1016/j.bbrep.2023.101635 |
| Related URLs: | |
| URI: | https://livrepository.liverpool.ac.uk/id/eprint/3178817 |
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