Synovial Fluid and Serum MicroRNA Signatures in Equine Osteoarthritis

The aim of this study was to identify differentially expressed microRNAs (miRNAs) in serum and synovial fluid (SF) samples of control horses and those with osteoarthritis (OA) to identify potential candidates for biomarkers of disease. Total RNA was extracted from serum and SF samples of control (n = 4) and OA (n = 9) horses and sequenced. Differential expression analysis, pathway analysis and miRNA target prediction were performed. A group of six miRNAs (eca-miR-199a-3p, eca-miR-148a, eca-miR-99b, eca-miR-146a, eca-miR-423-5p and eca-miR-23b) was selected for validation in an independent cohort (serum, n = 46; SF, n = 88). The effect of clinical variables on miRNA expression was also assessed. Sequencing analyses found 43 and 23 differentially expressed miRNAs in serum and SF samples, respectively. Pathway analysis showed miRNAs were involved in inflammatory disease/response and associated with OA pathways. miRNA expression in serum was strongly associated with the horses' workload, while age had a pronounced influence on miRNA expression in SF. Distinct patterns of miRNA differential expression were observed in serum and SF samples from horses with OA compared to controls. miR-199a-3p and miR-148a warrant further investigation as potential biomarkers of equine OA. Further characterization of these molecular changes could provide novel insights into the mechanisms of early OA.