Multi-Omic Temporal Landscape of Plasma and Synovial Fluid-Derived Extracellular Vesicles Using an Experimental Model of Equine Osteoarthritis.
Abstract: 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.
Publication Date: 2023-10-04 PubMed ID: 37834337PubMed Central: PMC10573509DOI: 10.3390/ijms241914888Google Scholar: Lookup
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Summary
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The research paper is about understanding how extracellular vesicles (EVs) found in synovial fluid and plasma contribute to the pathogenesis and progression of osteoarthritis, using an experimental model. It also explores the use of these vesicles as direct biomarkers for the disease.
Abstract: Introduction
- This research focuses on extracellular vesicles (EVs), which are tiny particles that cells release into their surrounding environment. These play vital roles in cell-to-cell communication and show significant influence in the progress of diseases, including osteoarthritis.
- Synovial fluid is a lubricating substance found in joints, and in the case of osteoarthritis, EVs from this fluid could provide critical information about the disease’s progression. They could potentially act as biomarkers – indicators of the presence and severity of the disease.
Methods and Analysis
- The research used a temporal model of osteoarthritis to track changes over time in the contents of EVs originating from synovial fluid and plasma. The small non-coding RNA and protein cargo of these EVs were studied using sequencing and mass spectrometry.
- The analysis incorporated several statistical and analytical tools. Time series clustering was used to group similar patterns over time; factor analysis studied the relationships between observed variables and latent variables; gene enrichment interrogation examined the overrepresentation of genes within a particular pathway.
Key Findings
- The protein cargo in the vesicles appeared more influential than small non-coding RNAs during osteoarthritis progression.
- The response of plasma-derived EVs to osteoarthritis was time-dependent and was linked to the creation of large complex structures (supramolecular complexes). On the other hand, synovial fluid-derived EVs were linked to the initial osteoarthritis response and represented immune/inflammatory pathways.
- Factor analysis revealed that the plasma-derived EVs were primarily composed of proteins regulating lipid metabolism. In contrast, the synovial fluid-derived EVs were linked to intermediate filament and supramolecular complexes, reflecting tissue repair processes.
- The researchers observed a significant interaction over time between osteoarthritis and various signaling aspects, as demonstrated by an increased influence of osteoarthritis synovial fluid-derived EVs at later stages of the disease.
Cite This Article
APA
Anderson JR, Johnson E, Jenkins R, Jacobsen S, Green D, Walters M, Bundgaard L, Hausmans BAC, van den Akker G, Welting TJM, Chabronova A, Kharaz YA, Clarke EJ, James V, Peffers MJ.
(2023).
Multi-Omic Temporal Landscape of Plasma and Synovial Fluid-Derived Extracellular Vesicles Using an Experimental Model of Equine Osteoarthritis.
Int J Mol Sci, 24(19), 14888.
https://doi.org/10.3390/ijms241914888 Publication
Researcher Affiliations
- Department of Musculoskeletal and Ageing Science, Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool L7 8TX, UK.
- Computational Biology Facility, Liverpool Shared Research Facilities, Faculty of Health and Life Sciences, University of Liverpool, Liverpool L7 8TX, UK.
- CDSS Bioanalytical Facility, Liverpool Shared Research Facilities, Department Pharmacology and Therapeutics, University of Liverpool, Liverpool L7 8TX, UK.
- Department of Veterinary Clinical Sciences, University of Copenhagen, Taastrup, DK-1870 Copenhagen, Denmark.
- Department of Musculoskeletal and Ageing Science, Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool L7 8TX, UK.
- Department of Veterinary Clinical Sciences, University of Copenhagen, Taastrup, DK-1870 Copenhagen, Denmark.
- Department of Veterinary Clinical Sciences, University of Copenhagen, Taastrup, DK-1870 Copenhagen, Denmark.
- Laboratory for Experimental Orthopedics, Department of Orthopedic Surgery, Maastricht University, 6229 Maastricht, The Netherlands.
- Laboratory for Experimental Orthopedics, Department of Orthopedic Surgery, Maastricht University, 6229 Maastricht, The Netherlands.
- Laboratory for Experimental Orthopedics, Department of Orthopedic Surgery, Maastricht University, 6229 Maastricht, The Netherlands.
- Department of Musculoskeletal and Ageing Science, Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool L7 8TX, UK.
- Department of Musculoskeletal and Ageing Science, Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool L7 8TX, UK.
- Department of Musculoskeletal and Ageing Science, Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool L7 8TX, UK.
- School of Veterinary Medicine and Science, University of Nottingham, Sutton Bonington, Loughborough, Nottingham LE12 5RD, UK.
- Department of Musculoskeletal and Ageing Science, Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool L7 8TX, UK.
MeSH Terms
- Animals
- Horses
- Synovial Fluid / metabolism
- Multiomics
- Osteoarthritis / metabolism
- Extracellular Vesicles / metabolism
- Models, Theoretical
Grant Funding
- 107471/Z/15/Z / Wellcome
- T15 / Horserace Betting Levy Board
- DFF - 7017-00066 / Independent Research Fund Denmark Technology and Production Sciences
Conflict of Interest Statement
The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.
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