Upregulation of miR-941 in Circulating CD14+ Monocytes Enhances Osteoclast Activation via WNT16 Inhibition in Patients with Psoriatic Arthritis

Abstract

Psoriatic arthritis (PsA) is a destructive joint disease mediated by osteoclasts. MicroRNAs (miRNAs) regulate several important pathways in osteoclastogenesis. We profiled the expression of miRNAs in CD14+ monocytes from PsA patients and investigated how candidate microRNAs regulate the pathophysiology in osteoclastogenesis. The RNA from circulatory CD14+ monocytes was isolated from PsA patients, psoriasis patients without arthritis (PsO), and healthy controls (HCs). The miRNAs were initially profiled by next-generation sequencing (NGS). The candidate miRNAs revealed by NGS were validated by PCR in 40 PsA patients, 40 PsO patients, and 40 HCs. The osteoclast differentiation and its functional resorption activity were measured with or without RNA interference against the candidate miRNA. The microRNA-941 was selectively upregulated in CD14+ monocytes from PsA patients. Osteoclast development and resorption ability were increased in CD14+ monocytes from PsA patients. Inhibition of miR-941 abrogated the osteoclast development and function while increased the expression of WNT16. After successful treatment, the increased miR-941 expression in CD14+ monocytes from PsA patients was revoked. The expression of miR-941 in CD14+ monocytes is associated with PsA disease activity. MiR-941 enhances osteoclastogenesis in PsA via WNT16 repression. The miR-941 could be a potential biomarker and treatment target for PsA.

Psoriatic Arthritis: Development, Detection and Prevention: A Scoping Review

“…In addition, MiR-21-5p upregulation in one of the mi-RNA signatures was identified in patients with active PsA and possibly might be used in the monitoring of response to treatment [32]. A similar role was suggested for miR-941, which was found in CD14+ monocytes [33].…”

In vitro osteoclastogenesis in autoimmune diseases – Strengths and pitfalls of a tool for studying pathological bone resorption and other disease characteristics

“…In research of human chronic inflammatory diseases, OC numbers are often consistent with total resorption, which is higher in RA versus HD PBM [ 25 , 69 ], in RA versus OA SFM [ 81 ], in PsA versus HD PBM [ 26 , 71 , 82 , 83 ] and in CD versus HD PBM [ 84 ]. Good concordance has been reported in comparison of erosive versus non-erosive RA, where both differentiation and resorption were higher in erosive RA PBM [ 69 ].…”

Advances of Genomic Medicine in Psoriatic Arthritis

“…Several studies have demonstrated differential expression of miRNAs that had previously been found to be altered in blood and synovial fluid samples from RA patients. For example, miRNA-146a and miRNA-941 expression is known to be upregulated in circulating CD14+ monocytes from PsA patients [56,57]. Pelosi et al identified in blood cells specific miRNA signatures associated with active and non-active disease.…”