Abstract
ABSTRACT
Background
Haemophilic arthropathy (HA) is a chronic joint disease in haemophiliac patients, driven by recurrent bleeding and distinct from osteoarthritis (OA) and rheumatoid arthritis (RA) in its pathogenesis, including metal ion accumulation and inflammatory responses.
Aim
To explore the role of metal ion binding proteins in HA and identify potential biomarkers and therapeutic targets.
Methods
Synovial tissues from 21 patients (7 HA, 7 OA, 7 RA) were analysed using data‐independent acquisition proteomics. Differentially expressed proteins were identified (fold change >2,
p
Results
HA synovial tissue showed 123 and 124 differentially expressed metal binding proteins versus OA and RA, respectively, with 29 overlapping proteins. Enriched functions included iron ion binding, magnesium ion binding, calcium ion binding, zinc ion binding and copper ion binding. Key pathways involved carbon metabolism, the TCA cycle, oxidative phosphorylation, and extracellular matrix remodelling. PPI analysis highlighted hub proteins, including SOD2, NDUFS1, ACO2, IDH3A, MMP1, COL1A1, COL1A2, and LOX. ICP‐MS confirmed elevated iron in HA tissues, and immunofluorescence validated protein expression trends.
Conclusion
Metal binding proteins are central to HA pathogenesis, influencing oxidative stress, mitochondrial function, and extracellular matrix remodelling. These findings provide potential biomarkers and therapeutic targets for synovial‐targeted regulation of metal ion homeostasis in HA.