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Home / Equine Research Bank / Biochem Biophys Rep / Proteome and phospholipidome interrelationship of synovial f...
Biochemistry and biophysics reports2024; 37; 101635; doi: 10.1016/j.bbrep.2023.101635

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

Abstract: 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 composite biomarker panel discovery. We here used a multi-omics strategy combining proteomics and phospholipidomics in an integral approach to identify composite biomarkers associated to purified extracellular vesicles from synovial fluid of healthy, mildly and severely osteoarthritic equine joints. Although the number of extracellular vesicles was unaffected by osteoarthritis, proteome profiling of extracellular vesicles by mass spectrometry identified 40 differentially expressed proteins (non-adjusted p < 0.05) in osteoarthritic joints associated with 7 significant canonical pathways in osteoarthritis. Moreover, pathway analysis unveiled changes in disease and molecular functions during osteoarthritis development. Phospholipidome profiling by mass spectrometry showed a relative increase in sphingomyelin and a decrease in phosphatidylcholine, phosphatidylinositol, and phosphatidylserine in extracellular vesicles derived from osteoarthritic joints compared to healthy joints. Unsupervised data integration revealed positive correlations between the proteome and the phospholipidome. Comprehensive analysis showed that some phospholipids and their related proteins increased as the severity of osteoarthritis progressed, while others decreased or remained stable. Altogether our data show interrelationships between synovial fluid extracellular vesicle-associated phospholipids and proteins responding to osteoarthritis pathology and which could be explored as potential composite diagnostic biomarkers of disease.
© 2024 The Authors.
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Publication Date: 2024-01-18 PubMed ID: 38298208PubMed Central: PMC10828605DOI: 10.1016/j.bbrep.2023.101635Google Scholar: Lookup
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Summary

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The research article discusses a ‘multi-omics’ study aimed at identifying potential composite biomarkers within synovial fluid-derived extracellular vesicles for diagnosing osteoarthritis in horses.

Research Context and Objective

  • Osteoarthritis is a debilitating condition that affects both humans and horses, leading to progressive joint deterioration, severe morbidity, and reduced mobility.
  • Current methods for diagnosing osteoarthritis are only effective during the late stages of the disease, and therefore, timely therapeutic intervention is often challenging.
  • The study aimed to address this issue by exploring cell-derived vesicles, known as extracellular vesicles, as potential sources for identifying specific composite biomarker panels. These vesicles play a significant role in cell-to-cell communication.

Research Approach and Findings

  • A multi-omics strategy was applied that combined proteomics (the study of proteins) and phospholipidomics (the study of phospholipids), enabling the researchers to identify composite biomarkers related to purified extracellular vesicles.
  • The study found that the number of extracellular vesicles was not affected by osteoarthritis. However, there was a change in the proteome profiling of these vesicles, with 40 different proteins being expressed differently in osteoarthritic joints. These changes were associated with seven significant canonical pathways of osteoarthritis.
  • Further analysis revealed changes in disease and molecular functions, indicating variations in the osteoarthritis development process.
  • Phospholipid profiling also showed changes, with a relative increase in sphingomyelin and a decrease in phosphatidylcholine, phosphatidylinositol, and phosphatidylserine in extracellular vesicles derived from osteoarthritic joints, compared to healthy joints.
  • An integration of data showed a positive correlation between the proteome and the phospholipidome. Comprehensive analysis revealed that as the severity of osteoarthritis progressed, some phospholipids and related proteins increased while others decreased or remained stable.

Significance of the Study

  • This research shows the interrelationships that exist between synovial fluid extracellular vesicle-associated proteins and lipids, influenced by osteoarthritis.
  • The results provide a new potential avenue to work on for early diagnosis using composite diagnostic biomarkers of osteoarthritis, potentially leading to timely and effective therapeutic interventions.

Cite This Article

APA
Clarke E, Varela L, Jenkins RE, Lozano-Andrés E, Cywińska A, Przewozny M, van Weeren PR, van de Lest CHA, Peffers M, Wauben MHM. (2024). Proteome and phospholipidome interrelationship of synovial fluid-derived extracellular vesicles in equine osteoarthritis: An exploratory ‘multi-omics’ study to identify composite biomarkers. Biochem Biophys Rep, 37, 101635. https://doi.org/10.1016/j.bbrep.2023.101635

Publication

Biochemistry and biophysics reports
ISSN: 2405-5808
NlmUniqueID: 101660999
Country: Netherlands
Language: English
Volume: 37
Pages: 101635

Researcher Affiliations

Clarke, Emily
  • Department of Musculoskeletal Biology and Ageing Science, Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool, UK.
Varela, Laura
  • Division Equine Sciences, Department of Clinical Sciences, Faculty of Veterinary Medicine, Utrecht University, Utrecht, the Netherlands.
  • Division Cell Biology, Metabolism & Cancer, Department of Biomolecular Health Sciences, Faculty of Veterinary Medicine, Utrecht University, Utrecht, the Netherlands.
Jenkins, Rosalind E
  • Centre for Drug Safety Science Bioanalytical Facility, Liverpool Shared Research Facilities, Department of Pharmacology and Therapeutics, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, UK.
Lozano-Andrés, Estefanía
  • Division Cell Biology, Metabolism & Cancer, Department of Biomolecular Health Sciences, Faculty of Veterinary Medicine, Utrecht University, Utrecht, the Netherlands.
  • Division of Infectious Diseases & Immunology, Department of Biomolecular Health Sciences, Faculty of Veterinary Medicine, Utrecht University, Utrecht, the Netherlands.
Cywińska, Anna
  • Faculty of Biological and Veterinary Sciences, Nicolaus Copernicus University in Torun, 87-100 Torun, Poland.
Przewozny, Maciej
  • EQUI VET SERWIS, Wygoda 6, 64-320, Buk, Poland.
van Weeren, P René
  • Division Equine Sciences, Department of Clinical Sciences, Faculty of Veterinary Medicine, Utrecht University, Utrecht, the Netherlands.
van de Lest, Chris H A
  • Division Equine Sciences, Department of Clinical Sciences, Faculty of Veterinary Medicine, Utrecht University, Utrecht, the Netherlands.
  • Division Cell Biology, Metabolism & Cancer, Department of Biomolecular Health Sciences, Faculty of Veterinary Medicine, Utrecht University, Utrecht, the Netherlands.
Peffers, Mandy
  • Department of Musculoskeletal Biology and Ageing Science, Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool, UK.
Wauben, Marca H M
  • Division Cell Biology, Metabolism & Cancer, Department of Biomolecular Health Sciences, Faculty of Veterinary Medicine, Utrecht University, Utrecht, the Netherlands.

Conflict of Interest Statement

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

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