Multi-Omic Temporal Landscape of Plasma and Synovial Fluid-Derived Extracellular Vesicles Using an Experimental Model of Equine Osteoarthritis

Anderson, James R.; Johnson, Emily; Jenkins, Rosalind; Jacobsen, Stine; Green, Daniel; Walters, Marie; Bundgaard, Louise; Hausmans, Bas A. C.; van den Akker, Guus; Welting, Tim J. M.; Chabronova, Alzbeta; Kharaz, Yalda A.; Clarke, Emily J.; James, Victoria; Peffers, Mandy J.

Abstract

Extracellular vesicles (EVs) contribute to osteoarthritis pathogenesis through their release into joint tissues and synovial fluid. Synovial fluid-derived EVs have the potential to be direct biomarkers in the causal pathway of disease but also enable understanding of their role in disease progression. Utilizing a temporal model of osteoarthritis, we defined the changes in matched synovial fluid and plasma-derived EV small non-coding RNA and protein cargo using sequencing and mass spectrometry. Data exploration included time series clustering, factor analysis and gene enrichment interrogation. Chondrocyte signalling was analysed using luciferase-based transcription factor activity assays. EV protein cargo appears to be more important during osteoarthritis progression than small non-coding RNAs. Cluster analysis revealed plasma-EVs represented a time-dependent response to osteoarthritis induction associated with supramolecular complexes. Clusters for synovial fluid-derived EVs were associated with initial osteoarthritis response and represented immune/inflammatory pathways. Factor analysis for plasma-derived EVs correlated with day post-induction and were primarily composed of proteins modulating lipid metabolism. Synovial fluid-derived EVs factors represented intermediate filament and supramolecular complexes reflecting tissue repair. There was a significant interaction between time and osteoarthritis for CRE, NFkB, SRE, SRF with a trend for osteoarthritis synovial fluid-derived EVs at later time points to have a more pronounced effect.

Citation

Anderson, J. R., Johnson, E., Jenkins, R., Jacobsen, S., Green, D., Walters, M., …Peffers, M. J. (2023). Multi-Omic Temporal Landscape of Plasma and Synovial Fluid-Derived Extracellular Vesicles Using an Experimental Model of Equine Osteoarthritis. International Journal of Molecular Sciences, 24(19), Article 14888. https://doi.org/10.3390/ijms241914888

• Journal Article Type: Article
• Acceptance Date: Sep 28, 2023
• Online Publication Date: Oct 4, 2023
• Publication Date: Oct 1, 2023
• Deposit Date: Oct 10, 2023
• Publicly Available Date: Oct 11, 2023
• Journal: International Journal of Molecular Sciences
• Print ISSN: 1661-6596
• Electronic ISSN: 1422-0067
• Publisher: MDPI
• Peer Reviewed: Peer Reviewed
• Volume: 24
• Issue: 19
• Article Number: 14888
• DOI: https://doi.org/10.3390/ijms241914888
• Keywords: Extracellular vesicles; osteoarthritis; multi-omics
• Public URL: https://nottingham-repository.worktribe.com/output/25685637