Multi-omic temporal landscape of plasma and synovial fluid-derived extracellular vesicles using an experimental model of equine osteoarthritis

• DOI: 10.1101/2023.08.01.551464
• Publication Date: 2023-08-02T05:10:18Z
• Authors: James R Anderson; Emily Johnson; Rosalind Jenkins; Stine Jacobsen; 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
• Keywords: Extracellular vesicles

Abstract Extracellular vesicles contribute to osteoarthritis pathogenesis through their release into joint tissues and synovial fluid. Limited studies have profiled extracellular in osteoarthritic biofluids, such as plasma Due the potential involvement pathogenesis, fluid-derived be ‘direct’ biomarkers causal pathway of disease but also enable understanding role progression. Utilizing a temporal model early osteoarthritis, we defined changes matched fluid plasma-derived vesicle small non-coding RNA protein cargo using sequencing mass spectrometry proteomics. We explored data with multi-omic approach including time series clustering, factor analysis gene enrichment interrogation. Chondrocyte signalling induced by derived from were analysed luciferase-based transcription activity assays. appears more important during progression than cargo. Cluster revealed plasma-extracellular represented time-dependant response induction, principally associated supramolecular complexes. Clusters for an initial immune/inflammatory pathways. Factor that correlated day post induction primarily composed proteins which may modulate lipid metabolism osteoarthritis. Synovial significant factors intermediate filament complexes reflecting tissue repair responses induction. There was interaction between cAMP element, Nuclear factor-kappa B serum element reporters trend EVs at later points pronounced effect. Local systemic osteoarthritis-associated profiles this vivo provided unique opportunity understand propagation represent novel stage