OBJECTIVE: MicroRNAs act locally and systemically to impact osteoarthritis pathophysiology, but comprehensive profiling of the circulating miRNome in early versus late stages of osteoarthritis has yet to be conducted. Our objective was to sequence the plasma miRNome from 91 patients with early [Kellgren-Lawrence grade 0 or 1 (n=41)] or late [Kellgren-Lawrence grade 3 or 4 (n=50)] symptomatic radiographic knee osteoarthritis to identify unique microRNA signatures in each disease state. MicroRNA libraries were prepared using the QIAseq miRNA Library Kit and sequenced on the Illumina NextSeq550. Counts were produced for microRNAs captured in miRBase and for novel microRNAs. Overall design: miRNA sequencing and analysis was performed using 91 plasma samples from patients with early and late radiographic knee OA.