007 Upregulation of miR-941 in peripheral CD14+ monocytes enhances osteoclast activation and osteolysis in patients with psoriatic arthritis: a potential diagnostic biomarker and treatment target

      In psoriatic arthritis (PsA), progressive bone destruction was mediated by osteoclasts differentiated from monocyte. MicroRNAs (miRNAs) regulate many pathophysiological processes, however, how they regulate osteoclast activation and bone resorption has not been examined. This study aims to address whether specific miRNAs in CD14+ monocytes and osteoclasts derived from them cause active osteoclastogenesis in PsA. The RNA from circulatory CD14+ monocytes was isolated from PsA patients, psoriatic patients without arthritis, and normal controls (NCs). The miRNA expressions were profiled by next-generation sequencing. The candidate miRNAs were validated by PCR in 32 PsA patients and 31 NCs. Osteoclasts were induced from CD14+ monocytes by TNF-α and RANKL. Osteoclast differentiation and bone resorption were measured by TRAP immunostaining and dentin slice resorption, respectively. The results showed that miR-941 was selectively upregulated in CD14+ monocytes from PsA patients. Activation and bone resorption were enhanced in osteoclasts from PsA patients, but both were abrogated by RNA interference against miR-941. After successful biologic treatment, the increased miR-941 expression in CD14+ monocytes from PsA patients was abrogated. However, osteoclastogenesis and resorption remained increased. Collectively, our findings suggest that miR-941 could be an early diagnostic potential biomarker, a dormant mediator leading to recurrence, and treatment niche for PsA.