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MiRNA sequencing of synovial fluid derived extracellular vesicles between normal and osteoarthritis (OA) patients

ABSTRACT: miRNA sequencing of synovial fluid derived extracellular vesicles between normal and osteoarthritis (OA) patients

PROVIDER: PRJNA522921 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR8586300.fastq.gz	Fastqsanger.gz
	SRR8586301.fastq.gz	Fastqsanger.gz
	SRR8586302.fastq.gz	Fastqsanger.gz
	SRR8586303.fastq.gz	Fastqsanger.gz
	SRR8586304.fastq.gz	Fastqsanger.gz

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miRNA sequencing of synovial fluid derived extracellular vesicles between normal and osteoarthritis (OA) patients

Project description:To determine whether extracellular vesicles were also present in human disease, we isolated and evaluated extracellular vesicles from synovial fluid from normal and OA patients at relatively advanced ages (70 - 80 years). Here we report the altered expression of synovial fluid extracellular vesicles-derived miRNAs in osteoarthritis compared to normal patients with age-relate degeneration to investigate potential biomarkers for OA diagnosis. The OA donors had clinical evidence of OA based on pain that led to total joint arthroplasty.

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Proteomics profiling of human synovial fluid suggests global increased protein interplay in early-osteoarthritis (OA) and lost in late-stage OA

Project description:The underlying molecular mechanisms in osteoarthritis (OA) development are largely unknown. This study explores the proteome and the pairwise interplay of proteins on a global level in synovial fluid from patients with late-stage knee OA (arthroplasty), early knee OA (arthroscopy due to degenerative meniscal tear) and from deceased controls without knee OA. Synovial fluid samples were analyzed using state-of-the-art mass spectrometry with data-independent acquisition. The differential expression of the proteins detected was clustered and evaluated with data mining strategies and a multilevel model. Group-specific slopes of associations were estimated between expressions of each pair of identified proteins to assess the co-expression (i.e. interplay) between the proteins in each group. More proteins were increased in early-OA vs controls than late-stage OA vs controls. For most of these proteins, the fold changes between late-stage OA vs controls and early stage OA vs controls were remarkably similar suggesting potential involvement in the OA process. Further, for the first time this study illustrated distinct patterns in protein co-expression suggesting that the global interplay between the protein machinery is increased in early-OA and lost in late-stage OA. Further efforts should probably focus on earlier stages of the disease than previously considered.

2022-01-27 | PXD023708 | Pride

Small non-coding RNAs in extracellular vesicles derived from equine synovial fluid and plasma in a model of equine osteoarthritis

Project description:We studied extracellular vesicles (EVs) from plasma and synovial fluid in an in vivo model of equine osteoarthritis by investigating longitudinal samples. EVs were isolated using size exclusion chromatography from plasma and synovial fluid of four horses subjected to an osteochondral fragment model of osteoarthritis at 0, 10, 35, 42, 49, 56, 63 days with relevant controls.EV RNA was extracted and subject to small RNA sequencing on an Illumina NovaSeq SP using 100bp, single end reads. After mapping against EquCab.3.0 and miRBase v22.1 differential expression analysis was undertaken with edgeRv3.28 using a quasi-likelihood negative binomial generalized log-linear model. We identified a panel of altered small non-coding RNAs.

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Project description:Synovial biopsies were obtained from osteoarthritis (OA) synovium to find genes upregulated during OA. The genes upregulated during OA can be used to identify disease characteristic genes. 10 microarrays of end-stage OA synovial biopsies were compared to 7 microarrays of synovial biopsies from individuals without a joint disease. Genes with >1.2-fold upregulation and P<0.05 in OA VS HC were selected from the analysis.

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

Project description: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.

2023-10-24 | PXD041515 | Pride

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Project description:Osteoarthritis (OA) is an aging-related degenerative joint disease without effective therapeutic. In the early stage of OA, mild synovitis has been proven to induce normal cartilage lesions. However, the mechanism is poorly defined. Here, we identified that the extracellular vesicles (EVs) derived from synovial inflammatory macrophages regulate the autophagy function of chondrocytes, acting as the dominant inducer of the onset of cartilage degeneration in normal and OA joints. Mechanistically, the active transfer of miR-155-5p via EVs from synovial inflammatory macrophages to chondrocytes accelerates cartilage degeneration by suppressing GSK 3β/mTORC1 axis-mediated autophagy function during OA progression.

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Synovial biopsies of osteoarthritis patients

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

Project description: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.

2024-05-24 | PXD042765 | Pride

Characterization of extracellular vesicles in plasma and synovial fluid of horses with naturally occurring post-traumatic osteoarthritis: An exploratory study to identify transcriptomic profiles.

Project description:Objective: The objective of this study was to characterize extracellular vesicles (EVs) in plasma and synovial fluid obtained from horses with and without naturally occurring post-traumatic osteoarthritis (PTOA). Animals (Samples): EVs were isolated from plasma and synovial fluid from horses with (n = 6) and without (n = 6) PTOA. Methods: Plasma and synovial fluid EVs were characterized with respect to quantity, size, and surface markers. Small RNA sequencing was performed and differentially expressed miRNAs underwent bioinformatic analysis to identify putative targets and to explore potential associations with specific biological processes. Results: Plasma and synovial fluid samples from horses with PTOA had a significantly higher proportion of exosomes and a lower proportion of microvesicles compared to horses without PTOA. Small RNA sequencing revealed several differentially expressed miRNAs including miR-144, miR-219-3p, and miR-199a-3p in plasma and miR-199a-3p, miR-214, and miR-9094 in synovial fluid EVs. Bioinformatics analysis of the differentially expressed miRNAs highlighted their potential role in fibrosis, differentiation of chondrocytes, apoptosis, and inflammation pathways in PTOA. Clinical Relevance: We have identified dynamic molecular changes in small non-coding signatures of plasma and synovial fluid EVs in horses with naturally occurring PTOA. These findings could serve to identify promising biomarkers in the pathogenesis of PTOA, to facilitate the development of targeted therapies, and to aid in establishing appropriate translational models of PTOA.

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