Biomarker and therapeutic applications of a novel microRNA in early-stage knee osteoarthritis

Abstract Osteoarthritis is a debilitating joint disease with no known cure, underscoring the need for early detection and intervention. Given their potential disease-specificity, novel microRNAs are promising biomarkers and therapeutic targets. Novel microRNAs are identified from sequencing data using bioinformatics analyses. Here we aimed to characterize a novel microRNA (novel_miRNA_2; UCCCUGUUCGGGCGCCACU) in knee osteoarthritis. We show circulating novel_miRNA_2 accurately distinguishes early-stage knee osteoarthritis from both non-osteoarthritis and late-stage knee osteoarthritis. In knee osteoarthritis subchondral bone, novel_miRNA_2 functions as a canonical microRNA, downregulating target genes such as RUNX2 . In male mice, novel_miRNA_2 mimic attenuates knee osteoarthritis when delivery begins in early stages, but not late stages. The decline in novel_miRNA_2 in late-stage knee osteoarthritis may be governed by Hedgehog signaling, which is known to upregulate genes such as RUNX2 and exacerbate osteoarthritis. Our findings suggest endogenous novel_miRNA_2 can be used to detect early-stage knee osteoarthritis when exogenous delivery can mitigate disease.