Dataset Information

Proteome and phospholipidome interrelationship of synovial fluid-derived extracellular vesicles in Equine osteoarthritis: An exploratory ‘multi-omic’ study

ABSTRACT: Osteoarthritis (OA) causes persistent joint deterioration, severe morbidity, and reduced mobility in both humans and horses. Extracellular vesicles (EVs) are key players in cell-to-cell communication and are thus ideal for biomarker discovery. Here, we used a unique multi-omics strategy to find possible EV biomarkers from the synovial fluid of healthy horses compared to naturally occurring OA and advanced OA. We discovered that SF-EVs’ proteome and phospholipidome are correlated. Furthermore, we found that the quantity of EVs present in SF was unaffected by OA. We discovered crucial signalling pathways involving integrins (p=2.72x10-24), the actin cytoskeleton (p=3.88x10-32), Rho family GTPases (p=1.24x10-19), and the clathrin-mediated endocytosis pathway (p=1.30x10-24). Specifically, the advanced OA group’s immunological response (macrophage binding and interaction) was upregulated. These findings are suggestive that the membrane and protein cargo of SF-EVs are altered in response to OA pathology and may be used as biomarkers of disease. Consequently, SF-EVs could have the potential to be employed in the future to help with OA stratification and prognosis. In addition, this study provides a framework for future research using a larger cohort.

INSTRUMENT(S): TripleTOF 6600

ORGANISM(S): Equus Caballus (horse)

TISSUE(S): Synovial Fluid

DISEASE(S): Osteoarthritis

SUBMITTER: Rosalind Jenkins

LAB HEAD: Rosalind Elspeth Jenkins

PROVIDER: PXD042765 | Pride | 2024-05-24

REPOSITORIES: Pride

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Dataset's files

Source:

			Action	DRS
	EJC_LVP_SF_EV10_SWATH_131222.wiff	Wiff
	EJC_LVP_SF_EV10_SWATH_131222.wiff.scan	Wiff
	EJC_LVP_SF_EV11_SWATH_131222.wiff	Wiff
	EJC_LVP_SF_EV11_SWATH_131222.wiff.scan	Wiff
	EJC_LVP_SF_EV12_SWATH_131222.wiff	Wiff

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Publications

Proteome and phospholipidome interrelationship of synovial fluid-derived extracellular vesicles in equine osteoarthritis: An exploratory 'multi-omics' study to identify composite biomarkers.

Clarke Emily E Varela Laura L Jenkins Rosalind E RE Lozano-Andrés Estefanía E Cywińska Anna A Przewozny Maciej M van Weeren P René PR van de Lest Chris H A CHA Peffers Mandy M Wauben Marca H M MHM

Biochemistry and biophysics reports 20240118

Osteoarthritis causes progressive joint deterioration, severe morbidity, and reduced mobility in both humans and horses. Currently, osteoarthritis is diagnosed at late stages through clinical examination and radiographic imaging, hence it is challenging to address and provide timely therapeutic interventions to slow disease progression or ameliorate symptoms. Extracellular vesicles are cell-derived vesicles that play a key role in cell-to-cell communication and are potential sources for specific ...[more]

PMID: 38298208

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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.