Abstract

ObjectivesIn 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.MethodsWith 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.ResultsSerum 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).ConclusionWe showed for the first time that miR-146a-5p and miR-186-5p are significantly associated with prevalent and incident knee OA, respectively.

Highlights

  • Osteoarthritis (OA) is the most frequent chronic musculoskeletal disease affecting approximately 40% of Rousseau et al Arthritis Research & Therapy [2]

  • Circulating miR-146a-5p is significantly associated with prevalent knee OA in women

  • Circulating miR-186-5p is significantly associated with incident knee OA in women

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Summary

Introduction

Osteoarthritis (OA) is the most frequent chronic musculoskeletal disease affecting approximately 40% of Rousseau et al Arthritis Research & Therapy [2]. Given the limitations of the tools that are currently available for OA assessment, there is considerable interest in the identification of specific biological markers that reflect quantitative and dynamic variations in joint tissue remodeling. For this purpose, microRNAs (miRNAs) are new potential targets. Several in vitro and in vivo studies have reported the miRNA involvement in the OA onset and progression, by targeting cartilage-associated genes [4] They regulate the expression of genes involved in pathways altered in OA chondrocytes such as apoptosis [5], expression levels of MMPs and ADAMTS [6,7,8], and chondrocyte signaling [9, 10]. The aberrant expression levels previously reported in circulating miRNAs differ considerably between clinical studies due to the different characteristics of these settings [14,15,16,17,18,19,20,21,22]

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