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International journal of molecular sciences2023; 24(19); 14888; doi: 10.3390/ijms241914888

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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  • Journal Article

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

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

ISSN: 1422-0067
NlmUniqueID: 101092791
Country: Switzerland
Language: English
Volume: 24
Issue: 19
PII: 14888

Researcher Affiliations

Anderson, James R
  • Department of Musculoskeletal and Ageing Science, Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool L7 8TX, UK.
Johnson, Emily
  • Computational Biology Facility, Liverpool Shared Research Facilities, Faculty of Health and Life Sciences, University of Liverpool, Liverpool L7 8TX, UK.
Jenkins, Rosalind
  • CDSS Bioanalytical Facility, Liverpool Shared Research Facilities, Department Pharmacology and Therapeutics, University of Liverpool, Liverpool L7 8TX, UK.
Jacobsen, Stine
  • Department of Veterinary Clinical Sciences, University of Copenhagen, Taastrup, DK-1870 Copenhagen, Denmark.
Green, Daniel
  • Department of Musculoskeletal and Ageing Science, Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool L7 8TX, UK.
Walters, Marie
  • Department of Veterinary Clinical Sciences, University of Copenhagen, Taastrup, DK-1870 Copenhagen, Denmark.
Bundgaard, Louise
  • Department of Veterinary Clinical Sciences, University of Copenhagen, Taastrup, DK-1870 Copenhagen, Denmark.
Hausmans, Bas A C
  • Laboratory for Experimental Orthopedics, Department of Orthopedic Surgery, Maastricht University, 6229 Maastricht, The Netherlands.
van den Akker, Guus
  • Laboratory for Experimental Orthopedics, Department of Orthopedic Surgery, Maastricht University, 6229 Maastricht, The Netherlands.
Welting, Tim J M
  • Laboratory for Experimental Orthopedics, Department of Orthopedic Surgery, Maastricht University, 6229 Maastricht, The Netherlands.
Chabronova, Alzbeta
  • Department of Musculoskeletal and Ageing Science, Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool L7 8TX, UK.
Kharaz, Yalda A
  • Department of Musculoskeletal and Ageing Science, Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool L7 8TX, UK.
Clarke, Emily J
  • Department of Musculoskeletal and Ageing Science, Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool L7 8TX, UK.
James, Victoria
  • School of Veterinary Medicine and Science, University of Nottingham, Sutton Bonington, Loughborough, Nottingham LE12 5RD, UK.
Peffers, Mandy J
  • 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.

References

This article includes 77 references
  1. Hunter DJ, Bierma-Zeinstra S. Osteoarthritis.. Lancet 2019;393:1745–1759.
    doi: 10.1016/S0140-6736(19)30417-9pubmed: 31034380google scholar: lookup
  2. Todhunter PG, Kincaid SA, Todhunter RJ, Kammermann JR, Johnstone B, Baird AN, Hanson RR, Wright JM, Lin HC, Purohit RC. Immunohistochemical analysis of an equine model of synovitis-induced arthritis.. Am. J. Vet. Res. 1996;57:1080–1093.
    pubmed: 8807026
  3. Ireland JL, Clegg PD, McGowan CM, McKane SA, Chandler KJ, Pinchbeck GL. Comparison of owner-reported health problems with veterinary assessment of geriatric horses in the United Kingdom.. Equine Vet. J. 2012;44:94–100.
  4. Little CB, Ghosh P, Rose R. The effect of strenuous versus moderate exercise on the metabolism of proteoglycans in articular cartilage from different weight-bearing regions of the equine third carpal bone.. Osteoarthr. Cartil. 1997;5:161–172.
    doi: 10.1016/S1063-4584(97)80011-8pubmed: 9219679google scholar: lookup
  5. Sanchez-Lopez E, Coras R, Torres A, Lane NE, Guma M. Synovial inflammation in osteoarthritis progression.. Nat. Rev. Rheumatol. 2022;18:258–275.
    doi: 10.1038/s41584-022-00749-9pmc: PMC9050956pubmed: 35165404google scholar: lookup
  6. Loeser RF. Molecular mechanisms of cartilage destruction: Mechanics, inflammatory mediators, and aging collide.. Arthritis Rheum. 2006;54:1357–1360.
    doi: 10.1002/art.21813pmc: PMC1774815pubmed: 16645963google scholar: lookup
  7. Junker S, Krumbholz G, Frommer KW, Rehart S, Steinmeyer J, Rickert M, Schett G, Muller-Ladner U, Neumann E. Differentiation of osteophyte types in osteoarthritis—Proposal of a histological classification.. Jt. Bone Spine. 2016;83:63–67.
    doi: 10.1016/j.jbspin.2015.04.008pubmed: 26076655google scholar: lookup
  8. Donell S. Subchondral bone remodelling in osteoarthritis.. EFORT Open Rev. 2019;4:221–229.
    doi: 10.1302/2058-5241.4.180102pmc: PMC6549114pubmed: 31210964google scholar: lookup
  9. Caron JP. Understanding the pathogenesis of equine osteoarthritis.. Br. Vet. J. 1992;148:369–371.
    doi: 10.1016/0007-1935(92)90023-Tpubmed: 1422780google scholar: lookup
  10. Goldring MB. Update on the biology of the chondrocyte and new approaches to treating cartilage diseases.. Best. Pract. Res. Clin. Rheumatol. 2006;20:1003–1025.
    doi: 10.1016/j.berh.2006.06.003pubmed: 16980220google scholar: lookup
  11. Kaur S, Abu-Shahba AG, Paananen RO, Hongisto H, Hiidenmaa H, Skottman H, Seppanen-Kaijansinkko R, Mannerstrom B. Small non-coding RNA landscape of extracellular vesicles from human stem cells.. Sci. Rep. 2018;8:15503.
    doi: 10.1038/s41598-018-33899-6pmc: PMC6195565pubmed: 30341351google scholar: lookup
  12. Ni Z, Zhou S, Li S, Kuang L, Chen H, Luo X, Ouyang J, He M, Du X, Chen L. Exosomes: Roles and therapeutic potential in osteoarthritis.. Bone Res. 2020;8:25.
    doi: 10.1038/s41413-020-0100-9pmc: PMC7305215pubmed: 32596023google scholar: lookup
  13. Withrow J, Murphy C, Liu Y, Hunter M, Fulzele S, Hamrick MW. Extracellular vesicles in the pathogenesis of rheumatoid arthritis and osteoarthritis.. Arthritis Res. Ther. 2016;18:286.
    doi: 10.1186/s13075-016-1178-8pmc: PMC5134070pubmed: 27906035google scholar: lookup
  14. Ragni E, Perucca Orfei C, De Luca P, Lugano G, Vigano M, Colombini A, Valli F, Zacchetti D, Bollati V, de Girolamo L. Interaction with hyaluronan matrix and miRNA cargo as contributors for in vitro potential of mesenchymal stem cell-derived extracellular vesicles in a model of human osteoarthritic synoviocytes.. Stem Cell Res. Ther. 2019;10:109.
    doi: 10.1186/s13287-019-1215-zpmc: PMC6440078pubmed: 30922413google scholar: lookup
  15. Clarke EJ, Johnson E, Caamano Gutierrez E, Andersen C, Berg LC, Jenkins RE, Lindegaard C, Uvebrant K, Lundgren-Akerlund E, Turlo A. Temporal extracellular vesicle protein changes following intraarticular treatment with integrin α10β1-selected mesenchymal stem cells in equine osteoarthritis.. Front. Vet. Sci. 2022;9:1057667.
    doi: 10.3389/fvets.2022.1057667pmc: PMC9730043pubmed: 36504839google scholar: lookup
  16. Cai J, Wu J, Wang J, Li Y, Hu X, Luo S, Xiang D. Extracellular vesicles derived from different sources of mesenchymal stem cells: Therapeutic effects and translational potential.. Cell Biosci. 2020;10:69.
    doi: 10.1186/s13578-020-00427-xpmc: PMC7245623pubmed: 32483483google scholar: lookup
  17. Li Z, Wang Y, Xiao K, Xiang S, Li Z, Weng X. Emerging Role of Exosomes in the Joint Diseases.. Cell. Physiol. Biochem. 2018;47:2008–2017.
    doi: 10.1159/000491469pubmed: 29969758google scholar: lookup
  18. Zhao Y, Xu J. Synovial fluid-derived exosomal lncRNA PCGEM1 as biomarker for the different stages of osteoarthritis.. Int. Orthop. 2018;42:2865–2872.
    doi: 10.1007/s00264-018-4093-6pubmed: 30128669google scholar: lookup
  19. Anderson JR, Jacobsen S, Walters M, Bundgaard L, Diendorfer A, Hackl M, Clarke EJ, James V, Peffers MJ. Small non-coding RNA landscape of extracellular vesicles from a post-traumatic model of equine osteoarthritis.. Front. Vet. Sci. 2022;9:901269.
    doi: 10.3389/fvets.2022.901269pmc: PMC9393553pubmed: 36003409google scholar: lookup
  20. Wijesinghe SN, Anderson J, Brown TJ, Nanus DE, Housmans B, Green JA, Hackl M, Choi KK, Arkill KP, Welting T. The role of extracellular vesicle miRNAs and tRNAs in synovial fibroblast senescence.. Front. Mol. Biosci. 2022;9:971621.
    doi: 10.3389/fmolb.2022.971621pmc: PMC9537453pubmed: 36213127google scholar: lookup
  21. Foers AD, Garnham AL, Chatfield S, Smyth GK, Cheng L, Hill AF, Wicks IP, Pang KC. Extracellular Vesicles in Synovial Fluid from Rheumatoid Arthritis Patients Contain miRNAs with Capacity to Modulate Inflammation.. Int. J. Mol. Sci. 2021;22:4910.
    doi: 10.3390/ijms22094910pmc: PMC8125513pubmed: 34066338google scholar: lookup
  22. Clarke EJ, Lima C, Anderson JR, Castanheira C, Beckett A, James V, Hyett J, Goodacre R, Peffers MJ. Optical photothermal infrared spectroscopy can differentiate equine osteoarthritic plasma extracellular vesicles from healthy controls.. Anal. Methods. 2022;14:3661–3670.
    doi: 10.1039/D2AY00779Gpmc: PMC9521322pubmed: 36066093google scholar: lookup
  23. Foers AD, Dagley LF, Chatfield S, Webb AI, Cheng L, Hill AF, Wicks IP, Pang KC. Proteomic analysis of extracellular vesicles reveals an immunogenic cargo in rheumatoid arthritis synovial fluid.. Clin. Transl. Immunol. 2020;9:e1185.
    doi: 10.1002/cti2.1185pmc: PMC7648259pubmed: 33204424google scholar: lookup
  24. Huang Y, Liu Y, Huang Q, Sun S, Ji Z, Huang L, Li Z, Huang X, Deng W, Li T. TMT-Based Quantitative Proteomics Analysis of Synovial Fluid-Derived Exosomes in Inflammatory Arthritis.. Front. Immunol. 2022;13:800902.
    doi: 10.3389/fimmu.2022.800902pmc: PMC8961740pubmed: 35359923google scholar: lookup
  25. Ripmeester EGJ, Caron MMJ, van den Akker GGH, Surtel DAM, Cremers A, Balaskas P, Dyer P, Housmans BAC, Chabronova A, Smagul A. Impaired chondrocyte U3 snoRNA expression in osteoarthritis impacts the chondrocyte protein translation apparatus.. Sci. Rep. 2020;10:13426.
    doi: 10.1038/s41598-020-70453-9pmc: PMC7417995pubmed: 32778764google scholar: lookup
  26. Peffers MJ, Chabronova A, Balaskas P, Fang Y, Dyer P, Cremers A, Emans PJ, Feczko PZ, Caron MM, Welting TJM. SnoRNA signatures in cartilage ageing and osteoarthritis.. Sci. Rep. 2020;10:10641.
    doi: 10.1038/s41598-020-67446-zpmc: PMC7326970pubmed: 32606371google scholar: lookup
  27. Chabronova A, van den Akker GGH, Housmans BAC, Caron MMJ, Cremers A, Surtel DAM, Wichapong K, Peffers MMJ, van Rhijn LW, Marchand V. Ribosomal RNA-based epitranscriptomic regulation of chondrocyte translation and proteome in osteoarthritis.. Osteoarthr. Cartil. 2023;31:374–385.
    doi: 10.1016/j.joca.2022.12.010pubmed: 36621590google scholar: lookup
  28. Baker ME, Lee S, Clinton M, Hackl M, Castanheira C, Peffers MJ, Taylor SE. Investigation of MicroRNA Biomarkers in Equine Distal Interphalangeal Joint Osteoarthritis.. Int. J. Mol. Sci. 2022;23:15526.
    doi: 10.3390/ijms232415526pmc: PMC9779011pubmed: 36555166google scholar: lookup
  29. Castanheira C, Anderson JR, Fang Y, Milner PI, Goljanek-Whysall K, House L, Clegg PD, Peffers MJ. Mouse microRNA signatures in joint ageing and post-traumatic osteoarthritis.. Osteoarthr. Cart. Cartil. Open. 2021;3:100186.
  30. Castanheira C, Balaskas P, Falls C, Ashraf-Kharaz Y, Clegg P, Burke K, Fang Y, Dyer P, Welting TJM, Peffers MJ. Equine synovial fluid small non-coding RNA signatures in early osteoarthritis.. BMC Vet. Res. 2021;17:26.
    doi: 10.1186/s12917-020-02707-7pmc: PMC7796526pubmed: 33422071google scholar: lookup
  31. Hulme CH, Peffers MJ, Harrington GMB, Wilson E, Perry J, Roberts S, Gallacher P, Jermin P, Wright KT. Identification of Candidate Synovial Fluid Biomarkers for the Prediction of Patient Outcome After Microfracture or Osteotomy.. Am. J. Sports Med. 2021;49:1512–1523.
    doi: 10.1177/0363546521995565pubmed: 33787363google scholar: lookup
  32. Hulme CH, Wilson EL, Peffers MJ, Roberts S, Simpson DM, Richardson JB, Gallacher P, Wright KT. Autologous chondrocyte implantation-derived synovial fluids display distinct responder and non-responder proteomic profiles.. Arthritis Res. Ther. 2017;19:150.
    doi: 10.1186/s13075-017-1336-7pmc: PMC5493128pubmed: 28666451google scholar: lookup
  33. Peffers MJ, Cillero-Pastor B, Eijkel GB, Clegg PD, Heeren RM. Matrix assisted laser desorption ionization mass spectrometry imaging identifies markers of ageing and osteoarthritic cartilage.. Arthritis Res. Ther. 2014;16:R110.
    doi: 10.1186/ar4560pmc: PMC4095688pubmed: 24886698google scholar: lookup
  34. Peffers MJ, McDermott B, Clegg PD, Riggs CM. Comprehensive protein profiling of synovial fluid in osteoarthritis following protein equalization.. Osteoarthr. Cartil. 2015;23:1204–1213.
    doi: 10.1016/j.joca.2015.03.019pmc: PMC4528073pubmed: 25819577google scholar: lookup
  35. Timur UT, Jahr H, Anderson J, Green DC, Emans PJ, Smagul A, van Rhijn LW, Peffers MJ, Welting TJM. Identification of tissue-dependent proteins in knee OA synovial fluid.. Osteoarthr. Cartil. 2021;29:124–133.
    doi: 10.1016/j.joca.2020.09.005pubmed: 33166667google scholar: lookup
  36. Anderson AR, Phelan MM, Caamano-Gutierrez E, Clegg PD, Rubio-Martinez LK, Peffers MJ. Metabolomic and Proteomic Stratification of Equine Osteoarthritis.. BioRxiv 2020.
    doi: 10.1101/2020.05.04.077305google scholar: lookup
  37. Walters M, Skovgaard K, Heegaard P, Peffers M, Fang Y, Bundgaard L, Skovgaard L, Jacobsen S. Changes in small non-coding RNA expression in synovial fluid during disease progression in an equine model of experimental osteoarthritis.. Osteoarthr. Cartil. 2021;29:S155–S156.
  38. Jin L, Bi Y, Hu C, Qu J, Shen S, Wang X, Tian Y. A comparative study of evaluating missing value imputation methods in label-free proteomics.. Sci. Rep. 2021;11:1760.
    doi: 10.1038/s41598-021-81279-4pmc: PMC7815892pubmed: 33469060google scholar: lookup
  39. Gardner ML, Freitas MA. Multiple Imputation Approaches Applied to the Missing Value Problem in Bottom-Up Proteomics.. Int. J. Mol. Sci. 2021;22:9650.
    doi: 10.3390/ijms22179650pmc: PMC8431783pubmed: 34502557google scholar: lookup
  40. Ashburner M, Ball CA, Blake JA, Botstein D, Butler H, Cherry JM, Davis AP, Dolinski K, Dwight SS, Eppig JT. Gene ontology: Tool for the unification of biology.. Nat. Genet. 2000;25:25–29.
    doi: 10.1038/75556pmc: PMC3037419pubmed: 10802651google scholar: lookup
  41. Burgelman M, Dujardin P, Vandendriessche C, Vandenbroucke RE. Free complement and complement containing extracellular vesicles as potential biomarkers for neuroinflammatory and neurodegenerative disorders.. Front. Immunol. 2022;13:1055050.
    doi: 10.3389/fimmu.2022.1055050pmc: PMC9896008pubmed: 36741417google scholar: lookup
  42. Park DJ, Duggan E, Ho K, Dorschner RA, Dobke M, Nolan JP, Eliceiri BP. Serpin-loaded extracellular vesicles promote tissue repair in a mouse model of impaired wound healing.. J. Nanobiotechnology. 2022;20:474.
    doi: 10.1186/s12951-022-01656-7pmc: PMC9636779pubmed: 36335351google scholar: lookup
  43. Karasu E, Eisenhardt SU, Harant J, Huber-Lang M. Extracellular Vesicles: Packages Sent With Complement.. Front. Immunol. 2018;9:721.
    doi: 10.3389/fimmu.2018.00721pmc: PMC5904200pubmed: 29696020google scholar: lookup
  44. Gu X, Chen A, Su Y, You M, Guo H, Tan S, He Q, Hu B. Extracellular vesicles: A new communication paradigm of complement in neurological diseases.. Brain Res. Bull. 2023;199:110667.
  45. Ahlmann-Eltze C, Anders S. ProDA: Probabilistic Dropout Analysis for Identifying Differentially Abundant Proteins in Label-Free Mass Spectrometry.. BioRxiv 2019;180:968–983.e24.
    doi: 10.1101/661496google scholar: lookup
  46. Argelaguet R, Arnol D, Bredikhin D, Deloro Y, Velten B, Marioni JC, Stegle O. MOFA+: A statistical framework for comprehensive integration of multi-modal single-cell data.. Genome Biol. 2020;21:111.
    doi: 10.1186/s13059-020-02015-1pmc: PMC7212577pubmed: 32393329google scholar: lookup
  47. Housmans BAC, van den Akker GGH, Neefjes M, Timur UT, Cremers A, Peffers MJ, Caron MMJ, van Rhijn LW, Emans PJ, Boymans T. Direct comparison of non-osteoarthritic and osteoarthritic synovial fluid-induced intracellular chondrocyte signaling and phenotype changes.. Osteoarthr. Cartil. 2023;31:60–71.
    doi: 10.1016/j.joca.2022.09.004pubmed: 36150677google scholar: lookup
  48. Raggi F, Bartolucci M, Cangelosi D, Rossi C, Pelassa S, Trincianti C, Petretto A, Filocamo G, Civino A, Eva A. Proteomic profiling of extracellular vesicles in synovial fluid and plasma from Oligoarticular Juvenile Idiopathic Arthritis patients reveals novel immunopathogenic biomarkers.. Front. Immunol. 2023;14:1134747.
    doi: 10.3389/fimmu.2023.1134747pmc: PMC10186353pubmed: 37205098google scholar: lookup
  49. Reymond S, Gruaz L, Sanchez JC. Depletion of abundant plasma proteins for extracellular vesicle proteome characterization: Benefits and pitfalls.. Anal. Bioanal. Chem. 2023;415:3177–3187.
    doi: 10.1007/s00216-023-04684-wpmc: PMC10287573pubmed: 37069444google scholar: lookup
  50. Cao X, Sandberg A, Araujo JE, Cvetkovski F, Berglund E, Eriksson LE, Pernemalm M. Evaluation of Spin Columns for Human Plasma Depletion to Facilitate MS-Based Proteomics Analysis of Plasma.. J. Proteome Res. 2021;20:4610–4620.
  51. Zhang X, Huebner JL, Kraus VB. Extracellular Vesicles as Biological Indicators and Potential Sources of Autologous Therapeutics in Osteoarthritis.. Int. J. Mol. Sci. 2021;22:8351.
    doi: 10.3390/ijms22158351pmc: PMC8347326pubmed: 34361116google scholar: lookup
  52. Mustonen AM, Lehmonen N, Paakkonen T, Raekallio M, Kakela R, Niemela T, Mykkanen A, Sihvo SP, Nieminen P. Equine osteoarthritis modifies fatty acid signatures in synovial fluid and its extracellular vesicles.. Arthritis Res. Ther. 2023;25:39.
    doi: 10.1186/s13075-023-02998-9pmc: PMC9996872pubmed: 36895037google scholar: lookup
  53. Mustonen AM, Lehmonen N, Oikari S, Capra J, Raekallio M, Mykkanen A, Paakkonen T, Rilla K, Niemela T, Nieminen P. Counts of hyaluronic acid-containing extracellular vesicles decrease in naturally occurring equine osteoarthritis.. Sci. Rep. 2022;12:17550.
    doi: 10.1038/s41598-022-21398-8pmc: PMC9585069pubmed: 36266410google scholar: lookup
  54. Watanabe H, Mokuda S, Tokunaga T, Kohno H, Ishitoku M, Araki K, Sugimoto T, Yoshida Y, Yamamoto T, Matsumoto M. Expression of factor XIII originating from synovial fibroblasts and macrophages induced by interleukin-6 signaling.. Inflamm. Regen. 2023;43:2.
    doi: 10.1186/s41232-022-00252-4pmc: PMC9817275pubmed: 36609460google scholar: lookup
  55. Raghu H, Cruz C, Rewerts CL, Frederick MD, Thornton S, Mullins ES, Schoenecker JG, Degen JL, Flick MJ. Transglutaminase factor XIII promotes arthritis through mechanisms linked to inflammation and bone erosion.. Blood 2015;125:427–437.
  56. Kolhe R, Owens V, Sharma A, Lee TJ, Zhi W, Ghilzai U, Mondal AK, Liu Y, Isales CM, Hamrick MW. Sex-Specific Differences in Extracellular Vesicle Protein Cargo in Synovial Fluid of Patients with Osteoarthritis.. Life 2020;10:337.
    doi: 10.3390/life10120337pmc: PMC7763294pubmed: 33321751google scholar: lookup
  57. Gkretsi V, Simopoulou T, Tsezou A. Lipid metabolism and osteoarthritis: Lessons from atherosclerosis.. Prog. Lipid. Res. 2011;50:133–140.
    doi: 10.1016/j.plipres.2010.11.001pubmed: 21115041google scholar: lookup
  58. Gentle IE. Supramolecular Complexes in Cell Death and Inflammation and Their Regulation by Autophagy.. Front. Cell. Dev. Biol. 2019;7:73.
    doi: 10.3389/fcell.2019.00073pmc: PMC6509160pubmed: 31131275google scholar: lookup
  59. Neefjes M, Housmans BAC, van den Akker GGH, van Rhijn LW, Welting TJM, van der Kraan PM. Reporter gene comparison demonstrates interference of complex body fluids with secreted luciferase activity.. Sci. Rep. 2021;11:1359.
    doi: 10.1038/s41598-020-80451-6pmc: PMC7809208pubmed: 33446782google scholar: lookup
  60. Wen AY, Sakamoto KM, Miller LS. The role of the transcription factor CREB in immune function.. J. Immunol. 2010;185:6413–6419.
    doi: 10.4049/jimmunol.1001829pmc: PMC5519339pubmed: 21084670google scholar: lookup
  61. Sotiropoulos A, Gineitis D, Copeland J, Treisman R. Signal-regulated activation of serum response factor is mediated by changes in actin dynamics.. Cell. 1999;98:159–169.
    doi: 10.1016/S0092-8674(00)81011-9pubmed: 10428028google scholar: lookup
  62. Frisbie DD, Kawcak CE, McIlwraith CW. Evaluation of the effect of extracorporeal shock wave treatment on experimentally induced osteoarthritis in middle carpal joints of horses.. Am. J. Vet. Res. 2009;70:449–454.
    doi: 10.2460/ajvr.70.4.449pubmed: 19335099google scholar: lookup
  63. Demichev V, Messner CB, Vernardis SI, Lilley KS, Ralser M. DIA-NN: Neural networks and interference correction enable deep proteome coverage in high throughput.. Nat. Methods. 2020;17:41–44.
    doi: 10.1038/s41592-019-0638-xpmc: PMC6949130pubmed: 31768060google scholar: lookup
  64. Housmans BAC, Neefjes M, Surtel DAM, Vitik M, Cremers A, van Rhijn LW, van der Kraan PM, van den Akker GGH, Welting TJM. Synovial fluid from end-stage osteoarthritis induces proliferation and fibrosis of articular chondrocytes via MAPK and RhoGTPase signaling.. Osteoarthr. Cartil. 2022;30:862–874.
    doi: 10.1016/j.joca.2021.12.015pubmed: 35176481google scholar: lookup
  65. Willforss J, Chawade A, Levander F. NormalyzerDE: Online Tool for Improved Normalization of Omics Expression Data and High-Sensitivity Differential Expression Analysis.. J. Proteome Res. 2019;18:732–740.
    doi: 10.1021/acs.jproteome.8b00523pubmed: 30277078google scholar: lookup
  66. Zhang X, Smits AH, van Tilburg GB, Ovaa H, Huber W, Vermeulen M. Proteome-wide identification of ubiquitin interactions using UbIA-MS.. Nat. Protoc. 2018;13:530–550.
    doi: 10.1038/nprot.2017.147pubmed: 29446774google scholar: lookup
  67. Law CW, Alhamdoosh M, Su S, Dong X, Tian L, Smyth GK, Ritchie ME. RNA-seq analysis is easy as 1-2-3 with limma, Glimma and edgeR.. F1000Res. 2016;5:1408.
  68. Rappoport N, Shamir R. Multi-omic and multi-view clustering algorithms: Review and cancer benchmark.. Nucleic Acids Res. 2018;46:10546–10562.
    doi: 10.1093/nar/gky889pmc: PMC6237755pubmed: 30295871google scholar: lookup
  69. Kumar L, Futschik ME. Mfuzz: A software package for soft clustering of microarray data.. Bioinformation. 2007;2:5–7.
    doi: 10.6026/97320630002005pmc: PMC2139991pubmed: 18084642google scholar: lookup
  70. Velten B, Braunger JM, Argelaguet R, Arnol D, Wirbel J, Bredikhin D, Zeller G, Stegle O. Identifying temporal and spatial patterns of variation from multimodal data using MEFISTO.. Nat. Methods. 2022;19:179–186.
    doi: 10.1038/s41592-021-01343-9pmc: PMC8828471pubmed: 35027765google scholar: lookup
  71. Wu T, Hu E, Xu S, Chen M, Guo P, Dai Z, Feng T, Zhou L, Tang W, Zhan L. clusterProfiler 4.0: A universal enrichment tool for interpreting omics data.. Innovation. 2021;2:100141.
    doi: 10.1016/j.xinn.2021.100141pmc: PMC8454663pubmed: 34557778google scholar: lookup
  72. Huang CY, Vesvoranan O, Yin X, Montoya A, Londono V, Sawatari Y, Garcia-Godoy F. Anti-Inflammatory Effects of Conditioned Medium of Periodontal Ligament-Derived Stem Cells on Chondrocytes, Synoviocytes, and Meniscus Cells.. Stem Cells Dev. 2021;30:537–547.
    doi: 10.1089/scd.2021.0010pubmed: 33757298google scholar: lookup
  73. Cosenza S, Ruiz M, Toupet K, Jorgensen C, Noël D. Mesenchymal stem cells derived exosomes and microparticles protect cartilage and bone from degradation in osteoarthritis.. Sci. Rep. 2021;7:16214.
    doi: 10.1038/s41598-017-15376-8pmc: PMC5701135pubmed: 29176667google scholar: lookup
  74. Hotham WE, Thompson C, Szu-Ting L, Henson FMD. The anti-inflammatory effects of equine bone marrow stem cell‐derived extracellular vesicles on autologous chondrocytes.. Veter. Rec. Open. 2021;8:e22.
    doi: 10.1002/vro2.22pmc: PMC8580791pubmed: 34795904google scholar: lookup
  75. Ni Z, Kuang L, Chen H, Xie Y, Zhang B, Ouyang J, Wu J, Zhou S, Chen L, Su N. The exosome-like vesicles from osteoarthritic chondrocyte enhanced mature IL-1beta production of macrophages and aggra-vated synovitis in osteoarthritis.. Cell Death Dis. 2019;10:522.
    pmc: PMC6614358pubmed: 31285423
  76. Liu X, Shortt C, Zhang F, Bater MQ, Cowman MK, Kirsch T. Extracellular Vesicles Released from Articular Chondrocytes Play a Major Role in Cell–Cell Communication.. J. Orthop. Res. 2019;38:731–739.
    doi: 10.1002/jor.24525pmc: PMC7071989pubmed: 31736104google scholar: lookup
  77. Zhang S, Chuah SJ, Lai RC, Hui JHP, Lim SK, Toh WS. MSC exosomes mediate cartilage repair by enhancing proliferation, attenuating apoptosis and modulating immune reactivity.. Biomaterials 2018;156:16–27.

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