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

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

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.

Original languageEnglish
Article number14888
JournalInternational Journal of Molecular Sciences (Online)
Issue number19
Number of pages24
Publication statusPublished - 2023

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© 2023 by the authors.

    Research areas

  • extracellular vesicles, multi-omics, osteoarthritis

ID: 375057300