Dataset Information

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

ABSTRACT: Osteoarthritis (OA) is the most common equine joint disease characterised by cartilage degradation and changes to other joint tissues severely effecting welfare and performance leading to early retirement. It results in substantial morbidity and mortality, but our understanding of the pathophysiological mechanisms involved is limited. There are no disease modifying therapeutics available, with OA medication offering symptomatic relief only. Early diagnosis is thus important, as substantial joint pathology is usually present at the time of clinical diagnosis. Thus, biomarkers of early-stage OA are actively sought, and among these, extracellular vesicles (EVs) are emerging as potential candidates. Here we use a SWATH MS approach to profile the protein cargo of EVs derived from equine plasma and synovial fluid.

INSTRUMENT(S): TripleTOF 6600

ORGANISM(S): Equus Caballus (horse)

TISSUE(S): Blood Plasma, Extracellular Vesicle, Synovial Tissue

DISEASE(S): Osteoarthritis

SUBMITTER: Rosalind Jenkins

LAB HEAD: Rosalind Elspeth Jenkins

PROVIDER: PXD041515 | Pride | 2023-10-24

REPOSITORIES: Pride

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Publications

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

Anderson James R JR Johnson Emily E Jenkins Rosalind R Jacobsen Stine S Green Daniel D Walters Marie M Bundgaard Louise L Hausmans Bas A C BAC van den Akker Guus G Welting Tim J M TJM Chabronova Alzbeta A Kharaz Yalda A YA Clarke Emily J EJ James Victoria V Peffers Mandy J MJ

International journal of molecular sciences 20231004 19

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. D ...[more]

PMID: 37834337

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Project description:Background: Acute coronary syndromes (ACS) are associated with aberrant gene expression and epigenetic mechanisms. In particular, de novo DNA methylation is typically linked to gene silencing, but its role in heart disease remains not fully understood. Extracellular vesicles (EVs) are active components in cellular communication for their ability to carry a plethora of signalling biomolecules, thus representing a promising new diagnostic/therapeutic approach in cardiovascular diseases (CVDs). Indeed, there is the need of novel biomarkers for ACS prediction and timely detection. Purpose: We hypothesized that specific epigenetic signals can be carried by EVs. In this regard, we isolated and characterized circulating EVs from ACS patients and evaluated their potential role to influence DNA methylation in target cells. Methods: Circulating EVs were recovered, by ultracentrifugation, from plasma samples of 19 ACS patients and 50 healthy subjects (HS). Nanoparticle tracking analysis (NTA) and western blot (WB) were used to confirm the EVs integrity and purity. Peripheral blood mononuclear cells (PBMCs) of volunteer donors were treated with both ACS and HS derived EVs and genomic DNA was extracted to perform epigenome wide analysis through Reduced Representation Bisulfite Sequencing. ShinyGO, PANTHER, and STRING tools were interrogated to perform GO and PPI network analyses. Flow Cytometry, qRT-PCR, and WB analysis were also performed to evaluate and validate both intra-vesicular and intra-cellular signals. Results: Plasma ACS-derived EVs showed a significant up-regulation of DNA methyltransferases (DNMTs) gene expression levels as compared to HS (P<0.001). Specifically, de novo methylation transcripts, as DNMT3A and DNMT3B were significantly increased in plasma ACS-EVs. DNA methylation analysis of PBMCs from volunteer donors treated with HS- and ACS-derived EVs showed that RNF166 and CCND3 genes resulted the most hyper- and hypo-methylated, respectively, after by ACS-EV treatment. In addition, PPI network analysis specifically evidenced the subnetwork with SRC, as a hub gene, connecting it to NOTCH1, FOXO3, CDC42, IKBKG, RXRA, DGKG, known as important genes already involved in the onset of CVDs. Surprising, other novel genes, BAIAP2, SYP, CHL1, and SHB, which were hypomethylated, were found significantly overexpressed in PBMCs (P<0.005), underlying the fundamental modulating properties of EV cargo in atherosclerosis. Conclusions: These findings support the significant role of ACS plasma-derived EVs, inducing de novo DNA methylation signals, and modulating specific signaling pathways in target cells.

Dataset Information

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

Publications

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

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