Circulating microRNA profiles in early-stage osteoarthritis and rheumatoid arthritis

Abstract

BackgroundOsteoarthritis (OA) and rheumatoid arthritis (RA) are prevalent forms of arthritis. Early detection of OA and RA is challenging with existing methods, which can delay effective management. MicroRNAs are small molecules that have emerged as promising disease biomarkers with the potential to improve early detection and differentiation of arthritis subtypes. In this study we aimed to identify distinct circulating microRNAs in plasma from individuals with early OA and early RA, using an unbiased microRNA-sequencing approach. MethodsPlasma samples were collected from three study groups including: (a) early OA (N=20), individuals with knee OA symptoms and radiographic Kellgren-Lawrence grade 0 or 1; (b) early RA (N=12), treatment-naive individuals with <6 months of RA symptoms in any joint; and (c) non-OA/RA (N=44), individuals with no history of arthritis. Of these, N=62 samples were subjected to microRNA-sequencing and analysis using a previously optimized pipeline. Exploratory analyses were followed by a stepwise filtering approach to shortlist both known (documented in miRBase v22.1) and novel (predicted using bioinformatics) microRNAs. Prioritized microRNAs were then validated via real-time qPCR (RT-qPCR) in N=14 independent samples. ResultsPrincipal component analyses revealed clustering of early OA versus both early RA and non-OA/RA groups, but not between early RA and non-OA/RA. In early OA, n=170 differentially expressed (DE) microRNAs were identified compared to both early RA and non-OA/RA, while no significant differences were found between early RA and non-OA/RA. Of these DE microRNAs, stepwise filtering and RT-qPCR validation identified dysregulation of six known microRNAs between early OA and early RA. Of these six microRNAs, two were upregulated in early OA, including hsa-miR-16-5p and hsa-miR-29c-3p, and four were upregulated in early RA, including hsa-miR-744-5p, hsa-miR-382-5p, hsa-miR-3074-5p, and hsa-miR-11400. Additionally, one novel microRNA sequence was found to be enriched in early OA and four in early RA. ConclusionWe identified a total of six known and five novel circulating microRNAs that differ between early OA and early RA individuals. Validation of these microRNAs in independent cohorts is warranted to establish their biomarker potential for distinguishing individuals with early OA versus early RA.