Plasma microRNA-320c as a Potential Biomarker for the Severity of Knee Osteoarthritis and Regulates cAMP Responsive Element Binding Protein 5 (CREB5) in Chondrocytes

血浆 microRNA-320c 作为膝关节骨关节炎严重程度的潜在生物标志物并调节软骨细胞中的 cAMP 反应元件结合蛋白 5 (CREB5)

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作者:Rongwei Zhou, Like Zhao, Qian Wang, Yongjing Cheng, Miao Song, Cibo Huang

Conclusion

Our results indicate that plasma miR-320c may serve as a potential novel predictor of the severity of knee OA and that miR-320c may play an important role in the pathogenesis of OA through inhibiting the cAMP pathway by targeting CREB5.

Methods

Forty knee OA patients and 20 healthy controls were enrolled. The levels of plasma miR-320c and plasma inflammatory cytokines were measured by real-time PCR or ELISA. Correlations of Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores and cytokine levels with the miR-320c expression level were evaluated by Pearson correlation analysis. Then, a receiver operating characteristic (ROC) curve was drawn to analyse the diagnostic value of miR-320c in OA. Finally, the interaction of miR-320c and cAMP responsive element binding protein 5 (CREB5) was determined using a luciferase reporter assay, and the effect of CREB5 on the cAMP pathway was assessed.

Objective

Osteoarthritis (OA) is a commonly known prevalent joint disease, with limited therapeutic

Results

The expression level of plasma miR-320c was significantly higher in OA patients than in healthy controls (p < 0.05). The increased plasma miR-320c level was positively correlated with the WOMAC score (r = 0.796, p < 0.001) and the plasma interleukin (IL)-1β (r = 0.814, p < 0.001) and IL-6 (r = 0.695, p < 0.001) levels in patients with OA. ROC curve analysis demonstrated the relatively high diagnostic accuracy of plasma miR-320c for OA. Furthermore, the luciferase reporter assay results showed that miR-320c regulates CREB5 expression by binding to the CREB5 3'-untranslated region. Moreover, suppression of CREB5 significantly reduced the expression levels of c-fos and c-jun.

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