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. In OA, studies investigating the altered expression of regulatory RNA that may be used clinically are scarce. MicroRNAs (miRs) are small non-coding RNAs of approximately 22 nucleotides in length that can silence gene expression by binding to complementary sequence on target messenger RNA transcripts resulting in translational repression or target degradation. They are easily accessible and stable. So, we studied the differential expression of circulating miRs in subjects with and without OA in the OFELY cohort.

Methods: The study group included French women belonging to the population-based cohort OFELY (Os des FEmmes de LYon). Expression levels of serum miR were measured in 10 healthy women without OA at any site (knee, lumbar spine, hip and hand) and in 10 women with a Kellgren & Lawrence score of 2 and 3 (early and intermediate knee OA) and OA at others sites. The evaluation of the OA disease was performed by radiography for spine disc degeneration and knee OA, by clinical examination for hand OA and by questionnaire for hip OA. These evaluations have been performed at the same visit, 8 years after recruitment of the cohort. Both groups were matched for age (healthy: 61.9 ± 3.03 and OA: 63.9 ± 3.4 p=0.17) and menopausal status. According to the manufacturer’s protocol (EXIQON, Denmark) for the Next Generation Sequencing (NGS) method, RNA isolation was performed from 400 µl of serum followed by the library preparation and amplification and the µRNA sequencing (Illumina platform). Measurements were expressed as Tags per million (TPM), which is a unit used to measure expression in NGS experiments. The number of reads for a particular miR is divided by the total number of mapped reads and multiplied by 1 million (Tags Per Million, TPM).

Results: We identified 421 miRs with an expression level ≥ 1 TPM and 241 with an expression level ≥ 10 TPM. When we compared the two groups, 22 miRs showed differential expression (p<0.05) between controls and OA patients. After Benjamini-Hochberg False Discovery Rate (FDR) correction has-miR-139-5p, has-miR-1299 and has-miR-200a-3p remained significantly different between OA patients and controls (p<0.05, FDR at 5%) (Table).

Conclusion: With a NGS screening approach, we identified 3 miRs that are differentially expressed in women suffering from OA compared to healthy women. The next step will be the measurement of these specific miRs in the entire cohort to determine the clinical utility of these markers.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/certain-serum-micro-rnas-are-associated-with-osteoarthritis/