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

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.

Significant Changes in Serum MicroRNAs after High Tibial Osteotomy in Medial Compartmental Knee Osteoarthritis: Potential Prognostic Biomarkers

“…Therefore, we believe that miR-29c-3p is not a relevant serum biomarker after HTO, although it may be related to OA progression. Rousseau et al evaluated the association between circulating miRNAs and knee OA in women and reported no significant changes in miR-29c-3p levels, consistent with our results [31]. Many studies have revealed the role of miR-424-5p in cell-or tissue-based OA [32].…”

The Clinical Potential of Circulating miRNAs as Biomarkers: Present and Future Applications for Diagnosis and Prognosis of Age-Associated Bone Diseases

“…Similarly, plasma levels of miR-126 have been found to be increased in OA vs. controls [112] and, after celecoxib treatment, decreased in non-clinical responders and increased in clinical responders [118]. Finally, higher plasma miR-186 levels have been detected both in OA vs. controls [112] and in incident OA over the next 4 years [117].…”

“…In conclusion, circulating miR-136 and the combination of miR-486-5p, miR-122-5p, and miR-19b-3 have the highest diagnostic potential in distinguishing OA patients from healthy controls [113,115]. Among the above-described validate miRNAs, levels of miR-146a have been found to be increased both in plasma of OA vs. controls [112] and in serum of prevalent knee OA vs. controls [117]; while considering OA who received celecoxib treatment, plasma levels of miR-146a have been found to be increased in non-clinical responders and decreased in clinical responders [118]. Similarly, plasma levels of miR-126 have been found to be increased in OA vs. controls [112] and, after celecoxib treatment, decreased in non-clinical responders and increased in clinical responders [118].…”

“…Interestingly, in a group of postmenopausal women, increased levels of circulating miR-146a-5p and miR-186-5p associate, respectively, with prevalent knee OA and knee OA incident over the next 4 years [117].…”

Osteoarthritis year in review: genetics, genomics, epigenetics

“…Given that OA is polygenic in nature, miRNA are seen as attractive therapeutic entities as they In women from the Os des Femmes de Lyon (OFELY) cohort, circulating miR-146a-5p and 186-5p were elevated in those with prevalent knee OA compared to healthy controls. In fact, the likelihood of prevalent knee OA increased with each quartile increase in serum miR-146a-5p [39]. Local levels of isoform miR-146a along with miR-140-5p were downregulated in human OA chondrocytes and associated with hypermethylation of the regulatory regions in these miRNAs [40].…”