Circulating microRNA profiles in early-stage osteoarthritis and rheumatoid arthritis

Osteoarthritis (OA) and rheumatoid arthritis (RA) are prevalent joint diseases, yet early diagnosis remains challenging with existing methods. Circulating microRNAs are promising biomarkers for detection and differentiation of arthritis subtypes. This study aimed to profile plasma microRNAs from early OA (N = 22), early RA (N = 12), and non-OA/RA (N = 50) individuals using microRNA-sequencing. Principal component analysis revealed distinct clustering of early OA from both early RA and non-OA/RA, but not for early RA and non-OA/RA. A total of 170 differentially expressed microRNAs were identified in early OA versus the other groups, with no significant differences found between early RA and non-OA/RA. Stepwise filtering followed by RT-qPCR validation in independent samples identified six microRNAs: miR-16-5p and miR-29c-3p were upregulated in early OA compared to both early RA and non-OA/RA, while miR-744-5p, miR-382-5p, miR-3074-5p, and miR-11400 were upregulated in early RA compared to the other two groups. Additionally, three novel microRNAs were identified using bioinformatic tools-one enriched in early OA and two in early RA. Target prediction and pathway analyses revealed that early OA microRNAs were linked to extracellular matrix degradation pathways, and early RA microRNAs were linked to immune signaling. These findings highlight six known and three novel circulating microRNAs with potential as biomarkers to distinguish early OA from early RA.