Background/Purpose:

Sensitive and specific blood biomarkers to detect the initial stages of osteoarthritis (OA) and to predict the future development of the disease are not available in clinical routine. Consequently, there is a considerable interest in the identification of new markers. The small non-coding microRNAs (miRs) are endogenous regulators of gene expression by binding to complementary sequence on target messenger RNA transcripts that results in translational repression or target degradation. The remarkable miR stability in biofluids has suggested their utility as non-invasive disease biomarkers. Thus the levels of 19 circulating miRs has been assessed in subjects with and without OA in the OFELY cohort.

Methods:

The study group for the measurement of serum miR expression included French postmenopausal women belonging to the population-based cohort OFELY (Os des FEmmes de LYon, n= 610). Firstly, we randomly selected 43 women with a prevalent knee OA (Kellgren & Lawrence score of 2 and 3; early and intermediate knee OA) with or without OA at others sites (lumbar spine, hip, hand) (age: 68.3 ± 6.6 years, body mass index (BMI): 26.6 ± 4.4 kg/m^-2) and 43 healthy women without OA at any site matched for age and BMI. Secondly, we randomly selected 23 women with incident knee OA over the next 4 years (age: 68.4 ± 8 years, BMI: 25.2 ± 4 kg/m^-2) and 25 healthy subjects without incident OA matched for age and BMI. We have selected 19 candidate miRs (let-7e-5p; 16-5p; 29a-3p, 29b-3p; 29c-3p; 93-5p; 126-3p; 132-3p; 139-5p; 146a-5p; 184; 186-5p; 195-5p; 199a-3p; 200a-3p; 345-5p; 375; 885-5p; 1299) for real-time PCR analysis on the basis of our previous Next Generation Sequencing study measuring all circulating miRs and on literature data. Total RNA was extracted from 200 µl of serum (RNA isolation biofluids, EXIQON). MiRs were reverse-transcribed and PCR was performed with custom TaqMan array microRNA cards on a QuantStudio 7 flex (Applied Biosystems). The expression levels were quantified after data normalization using miR-191-5p; 222-3p; 361-5p as endogenous controls and cel-miR-39-3p as qPCR quality control.

Results:

When considered as a continuous variable, miR-146a-5p was significantly increased in the group of prevalent OA compared with healthy subjects (RQ: relative quantification; median [IQR]: 1.12 [0.73; 1.46] RQ vs 0.85 [0.62; 1.03] RQ, p=0.015 respectively). Using logistic regression analysis, the risk of OA prevalence was significantly increased (odds-ratio [95% CI]: 1.83 [1.21-2.77], p=0.004) for each quartile increase in serum miR-146a-5p. Moreover, there was a significant association between baseline miR-186 levels and the risk of incident knee OA for each quartile increase (odds-ratio [95% CI]: 1.71 [1.00-2.95], p=0.049).

Conclusion:

We have shown that miR-146a-5p is increased in women suffering from mild to moderate OA compared to healthy women. Importantly, miR-186 is also increased in those women who will develop radiographic knee OA over the next 4 years, therefore with the potential to detect preclinical knee OA.

« Back to 2017 ACR/ARHP Annual Meeting

ACR Meeting Abstracts - https://acrabstracts.org/abstract/association-of-circulating-micrornas-with-prevalent-and-incident-osteoarthritis-in-women-the-ofely-study/