Multi-Omic Temporal Landscape of Plasma and Synovial Fluid-Derived Extracellular Vesicles Using an Experimental Model of Equine Osteoarthritis
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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.
Originalsprog | Engelsk |
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Artikelnummer | 14888 |
Tidsskrift | International Journal of Molecular Sciences (Online) |
Vol/bind | 24 |
Udgave nummer | 19 |
Antal sider | 24 |
ISSN | 1661-6596 |
DOI | |
Status | Udgivet - 2023 |
Bibliografisk note
Funding Information:
This study and JA were funded by the Horserace Betting Levy Board (T15). MP was funded by Wellcome Trust Clinical. Intermediate Fellowship (grant 107471/Z/15/Z). LB and the animal experiment were funded by the Independent Research Fund Denmark, Technology and Production Sciences (grant number DFF-7017-00066, 2017) and Gerda and AageHaensch’s Foundation. MW was funded by a Ph.D. scholarship jointly awarded by the University of Copenhagen, the Technical University of Denmark, and the Swedish University of Agricultural Science.
Publisher Copyright:
© 2023 by the authors.
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