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The following is a summary of “EPO promotes the progression of rheumatoid arthritis by inducing desialylation via increasing the expression of neuraminidase 3,” published in the January 2024, issue of Rheumatology by Wu et al.

Researchers conducted a retrospective study to interpret the role and mechanism of erythropoietin (EPO) in rheumatoid arthritis (RA) progression, particularly its impact as an erythrocyte-stimulating factor, considering its increased levels in RA patients.

They determined the levels of EPO in serum and synovial fluid from both RA patients and healthy controls. Collagen-induced arthritis (CIA) mice were generated to validate EPO’s role in RA pathogenesis. Transcriptome sequencing was employed to identify differentially expressed genes (DEGs) in EPO-treated fibroblast-like synoviocytes (FLS). The transcription factor activity of neuraminidase 3 (NEU3) among the DEGs was confirmed through double luciferase reporting, DNA pulldown, electrophoretic mobility shift assay, and chromatin immunoprecipitation-quantitative PCR (qPCR) assays.

The results showed that EPO overexpression was confirmed in RA patients, exhibiting a positive correlation with Disease Activity Score 28-joint count. EPO intervention notably exacerbated joint destruction in CIA models. Transcriptome sequencing and qPCR confirmed the upregulation of NEU3 in EPO-treated FLS, with signal transducer and activator of transcription 5 identified as the specific transcription factor of NEU3. EPO upregulated NEU3 expression by activating the Janus kinase 2 (JAK2)-STAT5 signaling pathway via its receptor EPOR, promoting desialylation and enhancing FLS migration and invasion capabilities. This effect was validated using JAK2 inhibitor and NEU3 inhibitor assays.

Investigators concluded that EPO, as a proinflammatory factor, exacerbates RA progression by upregulating NEU3 expression via the JAK2/STAT5 pathway.

Source: ard.bmj.com/content/early/2024/01/25/ard-2023-224852