POS0230 THE miR-320 FAMILY IS UPREGULATED IN FAST-PROGRESSING RADIOGRAPHIC KNEE OSTEOARTHRITIS: DATA FROM THE OSTEOARTHRITIS INITIATIVE

Background There is an outstanding need for prognostic biomarkers to reliably detect fast-progressing knee osteoarthritis (OA) such that preventative interventions can be targeted this patient population. MicroRNA-sequencing unbiased approach comprehensive profiling of circulating microRNAs in liquid biopsies discover novel disease. As negative regulators gene expression, hold potential not only as biomarkers, but also mechanistic drivers OA. Objectives To apply microRNA-sequencing identify unique distinguish radiographic OA from both slow- and non-progressing Methods Leveraging the Osteoarthritis Initiative (OAI) longitudinal cohort, we applied our customized pipeline [1] blood plasma samples collected at baseline 4-year follow-up 106 participants. The disease trajectory each participant was constructed by plotting their Kellgren-Lawrence (KL) grades over 8-year period. Based on these trajectories, defined fast-progression increase KL 0/1 3/4 follow-up, slow-progression 2/3/4 non-progression no KL0/1 throughout follow-up. Following differential expression analysis, assessed predictive performance identified putative targets prioritized microRNAs. Results Comparing fast-progressors slow-progressors non-progressors, differentially expressed within timepoints (i.e., 48 2 follow-up) across timepoints. Among were four members miR-320 family, with miR-320d showing timepoints, compared non-progressors. models included had good accuracy (area under receiver operating characteristic curves ranging 82.6 91.9) distinguishing fast-progressors. Putative family 14-3-3 (Table 1), including YWHAE , whose downregulation cartilage reported promote deterioration [2]. Table 1. Predicted include family. member hsa-miR-320b hsa-miR-320c hsa-miR-320d hsa-miR-320e SFN M L YWHAB V H YWHAG YWHAH YWHAQ YWHAZ All mirDIP results bold text indicating prediction among top 1% microRNA/gene target pair. Letters denote score class V=very high, H=high, M=medium, L=low. Conclusion This study first its kind, two participants data-driven construction trajectories. We associated time. While data suggest microRNA could have applications OA, regulating impact severity, validation findings independent cohorts required. References [1]Potla P, Ali SA, Kapoor M. A bioinformatics analysis. Cartilage Open. 2021;3(1):100131. doi: https://doi.org/10.1016/j.ocarto.2020.100131 . [2]Fu W, Hettinghouse A, Chen Y, Hu Ding X, M, Mundra J, Song Liu R, Yi YS, Attur Samuels Strauss E, Leucht Schwarzkopf CJ. epsilon intracellular component TNFR2 receptor complex activation protects against osteoarthritis. Ann Rheum Dis. 2021 Dec;80(12):1615-1627. 10.1136/annrheumdis-2021-220000. Disclosure Interests None declared