Multi-Omic Temporal Landscape of Plasma and Synovial Fluid-Derived Extracellular Vesicles Using an Experimental Model of Equine Osteoarthritis
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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.
In: International Journal of Molecular Sciences (Online), Vol. 24, No. 19, 14888, 2023.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Multi-Omic Temporal Landscape of Plasma and Synovial Fluid-Derived Extracellular Vesicles Using an Experimental Model of Equine Osteoarthritis
AU - Anderson, James R.
AU - Johnson, Emily
AU - Jenkins, Rosalind
AU - Jacobsen, Stine
AU - Green, Daniel
AU - Walters, Marie
AU - Bundgaard, Louise
AU - Hausmans, Bas A.C.
AU - van den Akker, Guus
AU - Welting, Tim J.M.
AU - Chabronova, Alzbeta
AU - Kharaz, Yalda A.
AU - Clarke, Emily J.
AU - James, Victoria
AU - Peffers, Mandy J.
N1 - Publisher Copyright: © 2023 by the authors.
PY - 2023
Y1 - 2023
N2 - 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.
AB - 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.
KW - extracellular vesicles
KW - multi-omics
KW - osteoarthritis
U2 - 10.3390/ijms241914888
DO - 10.3390/ijms241914888
M3 - Journal article
C2 - 37834337
AN - SCOPUS:85174709086
VL - 24
JO - International Journal of Molecular Sciences (Online)
JF - International Journal of Molecular Sciences (Online)
SN - 1661-6596
IS - 19
M1 - 14888
ER -
ID: 375057300