Sequencing identifies a distinct signature of circulating microRNAs in early radiographic knee osteoarthritis

Summary 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. Sequencing has emerged as the preferred method for microRNA profiling since it offers high sensitivity and specificity. Our objective is to sequence the miRNome in plasma 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. Design 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. Statistical, bioinformatics, and computational biology approaches were used to refine and interpret the final list of microRNAs. Results From 215 differentially expressed microRNAs (FDR Conclusion Applying sequencing to well-characterized patient cohorts produced unbiased profiling of the circulating miRNome and identified a unique panel of 11 microRNAs in early radiographic knee osteoarthritis.