Abstract

ObjectivesTo compare the proteomics of synovial fluid (SF)-derived exosomes in rheumatoid arthritis (RA), axial spondyloarthritis (axSpA), gout, and osteoarthritis (OA) patients.MethodsExosomes were separated from SF by the Exoquick kit combined ultracentrifugation method. Tandem mass tags (TMT)-labeled liquid chromatography mass spectrometry (LC-MS/MS) technology was used to analyze the proteomics of SF-derived exosomes. Volcano plot, hierarchical cluster, gene ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were conducted.ResultsA total of 1,678 credible proteins were detected. Sixty-nine differentially expressed proteins were found in gout, compared with OA, axSpA, and RA simultaneously. Twenty-five proteins were found highly expressed in gout uniquely, lysozyme C and protein S100-A9 included, whose bioinformatic analysis was significantly involved in “neutrophil degranulation” and “prion diseases”. Eighty-four differentially expressed proteins were found in axSpA, compared with OA, gout, and RA simultaneously. Thirty-nine proteins were found highly expressed in axSpA uniquely, RNA-binding protein 8A and protein transport protein Sec24C included, whose bioinformatic analysis was significantly involved in “acute-phase response” and “citrate cycle”. One hundred and eighty-four differentially expressed proteins were found in RA, compared with OA, gout, and axSpA simultaneously. Twenty-eight proteins were found highly expressed in RA uniquely, pregnancy zone protein (PZP) and stromelysin-1 included, whose bioinformatic analysis was significantly involved in “serine-type endopeptidase inhibitor activity” and “complement and coagulation cascades”. Enzyme-linked immunosorbent assay (ELISA) result showed that the exosome-derived PZP level of SF in RA was higher than that in OA (p < 0.05).ConclusionOur study for the first time described the protein profiles of SF-derived exosomes in RA, axSpA, gout, and OA patients. Some potential biomarkers and hypothetical molecular mechanisms were proposed, which may provide helpful diagnostic and therapeutic insights for inflammatory arthritis (IA).

Highlights

  • Inflammatory arthritis (IA) is characterized by synovial inflammation and synovial hyperplasia leading to joint damage, and mainly includes gout, axial spondyloarthritis, and rheumatoid arthritis (RA) [1, 2]

  • The serum uric acid level of gout was higher than OA

  • The serum uric acid (sUA) levels of axial spondyloarthritis (axSpA) and RA were lower than OA

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Summary

Introduction

Inflammatory arthritis (IA) is characterized by synovial inflammation and synovial hyperplasia leading to joint damage, and mainly includes gout, axial spondyloarthritis (axSpA), and rheumatoid arthritis (RA) [1, 2]. It is of great importance to explore the pathogenesis and distinguishing biomarkers of IA. When patients suffer from IA, the volume and composition of SF would change. Immune cells, such as macrophages, lymphocytes, and neutrophils in the SF, would be activated and produce inflammatory cytokines and proteolytic enzymes, playing an important role in immune responses and bone destruction [7, 8]. Exosomes in SF have a close relationship with the pathogenesis of arthritis, which can lead to inflammation, degeneration of cartilage, and destruction of joints [10]. Recent studies showed that SF-derived exosomes can be the biomarker for different stages of joint disease [12]. No study has compared the proteomics of SF-derived exosomes in RA, axSpA, gout, and OA patients simultaneously

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