Association of circulating microRNAs with prevalent and incident knee osteoarthritis in women: The OFELY study

Abstract

Objectives: In the context of the scarcity of biomarkers for knee osteoarthritis (OA), we examined the associations of prevalent and incident OA with the expression levels of serum miRNAs in subjects with and without OA. Methods: With a next-generation sequencing approach, we compared the miRome expression of 10 women with knee OA and 10 age-matched healthy subjects. By real-time qPCR, we analyzed the expression levels of 19 miRNAs at baseline selecting 43 women with prevalent knee OA (Kellgren Lawrence score of 2/3), 23 women with incident knee OA over a 4-year follow-up and 67 healthy subjects without prevalent or incident OA matched for age and body mass index. Results: Serum miR-146a-5p was significantly increased in the group of prevalent knee OA compared with controls (relative quantification (RQ); median [Interquartile range] 1.12 [0.73; 1.46] vs 0.85 [0.62; 1.03], p = 0.015). The likelihood of prevalent knee OA was significantly increased (odds ratio [95% confidence interval (CI)] 1.83 [1.21-2.77], p = 0.004) for each quartile increase in serum miR-146a-5p. The women with miR-146a-5p levels above the median (0.851) had a higher risk of prevalent knee OA compared to those below the median [95% CI] 4.62 [1.85-11.5], p = 0.001. Moreover, we found a significant association between the baseline level of serum miR-186-5p and the risk of incident knee OA (Q4 vs Q1-3; odds ratio [95% CI] 6.13 [1.14-32.9], p = 0.034). Conclusion: We showed for the first time that miR-146a-5p and miR-186-5p are significantly associated with prevalent and incident knee OA, respectively.