Elevated Nesfatin-1 Level in Synovium and Synovial Fluid is Associated with Pro-Inflammatory Cytokines in Patients with Rheumatoid Arthritis

Abstract

Background: Adipocytokines have been proven to be involved in the progression of autoimmune diseases, including rheumatoid arthritis (RA). Nesfatin-1, a newly discovered adipokine, has recently been reported to possess potent anti-inflammatory, antiapoptotic, and antioxidative properties. However, its role in RA has not yet been reported. Therefore, this study aimed to determine nesfatin-1 levels in the synovium and synovial fluid (SF) of patients with RA and examine their correlation with clinical manifestations and proinflammatory cytokine levels. Methods: Synovium and SF samples were collected from patients with RA and non-RA patients during joint surgery. Immunohistochemistry was used to measure nesfatin-1 protein expression in the synovium. Enzyme-linked immunosorbent assay was used to measure nesfatin-1, interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α) levels in the synovium and SF. Pearson correlation analysis was used to evaluate the correlations between nesfatin-1 levels, RA clinical features, and proinflammatory cytokines. The diagnostic value of synovium nesfatin-1 for RA was assessed using receiver operating characteristic (ROC) curve analysis. Results: The results showed that nesfatin-1, IL-1β, and TNF-α levels in the synovium were significantly higher in patients with RA than in controls, with age and body mass index as covariates. Moreover, the results of Pearson correlation analysis showed that nesfatin-1 levels were positively correlated with IL-1β and TNF-α levels in the synovium of patients with RA. Furthermore, there was a positive relationship between synovium nesfatin-1 levels and rheumatoid factor in patients with RA. Additionally, the results of the ROC curve analysis revealed an area under the curve of 0.733 with 77.5% sensitivity and 60.0% specificity for synovium nesfatin-1 in discriminating patients with RA from controls. Conclusion: These findings suggest that increased nesfatin-1 levels in the synovium may be associated with proinflammatory cytokines and RA severity.

Nesfatin-1 stimulates CCL2-dependent monocyte migration and M1 macrophage polarization: implications for rheumatoid arthritis therapy

“…Several adipokines are implicated as risk factors of RA (20), including nesfatin-1 in particular, a serum marker of RA (21). Levels of nesfatin-1 expression in human RA synovium and synovial uid correlate with RA severity (22). Our analysis of human synovial tissue from the Gene Expression Omnibus (GEO) database records revealed high levels of nesfatin-1 expression in RA patients compared with healthy individuals.…”

Inhibition of NUCB2 suppresses the proliferation, migration, and invasion of rheumatoid arthritis synovial fibroblasts from patients with rheumatoid arthritis in vitro

“…For better comprehension of the nesfatin-1 signaling pathways, identification, localization, and modulation of the nesfatin-1 receptor will be essential. We have previously shown that increased nesfatin-1 levels in the synovium may be associated with the severity of disease in patients with RA [15]. To the best of our knowledge, the effect of NUCB2 inhibition on the tumorlike transformation of RASF has not been reported.…”

Nesfatin-1 Stimulates CCL2-dependent Monocyte Migration And M1 Macrophage Polarization: Implications For Rheumatoid Arthritis Therapy

“…Recent investigations have identified that nesfatin-1 participates in many different diseases and that this neuropeptide is a serum marker for RA 22 . Levels of nesfatin-1 expression in human RA synovium and synovial fluid correlate with RA severity 23 . Our analysis of human synovial tissue from the Gene Expression Omnibus (GEO) database records revealed high levels of nesfatin-1 expression in RA patients compared with healthy individuals.…”