Study On Pathogenesis And Potential Therapeutic Targets Of Hemophiliac Arthropathy Based On Proteomics

Background: Synovial hypertrophy and hyperplasia play an essential role in developing hemophilic arthropathy(HA).To better understand the molecular basis of synovial hypertrophy and hyperplasia in HA,we compared the proteomic profiles of HA with that of OA(Osteoarthritis)and RA(Rheumatoid arthritis).Methods: In this study,we collected synovial tissue samples from 14 hemophilic patients with osteoarthropathy(HA,OA,and RA).Synovial tissue samples of HA were collected for the first time in data-independent acquisition(DIA)mode by mass spectrometry,with OA and RA as control groups.Gene ontology(GO)analysis,KEGG pathway analysis,and protein interaction analysis were used to explore the functions and biological pathways of the differentially expressed proteins.The differentially expressed proteins OTUD6 B and MMP3 were verified by Western blot(WB)and immunohistochemistry(IHC).Results: A total of 80931 peptides and 6151 proteins were quantified.The results showed that 126 proteins were up-regulated and 815 were down-regulated in HA compared to OA.Compared with RA,196 proteins were up-regulated,and 997 were down-regulated in HA.Metabolic pathways,metal ion binding,and oxidative phosphorylation were significantly altered in HA synovium.Western blot(WB)and immunohistochemistry(IHC)confirmed the increased expression of OTUD6 B and the decreased expression of MMP3 in HA.Conclusions: This study reveals the changes in protein expression during the development of HA and provides new clues for the pathogenesis of synovial hypertrophy and hyperplasia in HA.