MicroRNA and Psoriatic Arthritis

Psoriatic Arthritis (PsA) is a chronic autoimmune disease characterised by synovial inflammation and progressive destruction of articular cartilage and bone, with significant impact on quality of life. While advances in therapies have dramatically improved prognosis, a significant proportion of patients do not respond, have sub-optimally responses or experience adverse events. Hence, a greater understanding of the underlying pathogenesis of PsA is required to develop new treatment strategies and improve disease outcomes. In recent years, endogenous short RNA molecules, the microRNAs, have attracted much attention as key post-transcriptional regulators controlling gene expression under homeostatic and inflammatory conditions. In this research programme we are examining the effect of specific microRNA on proinflammatory mechanisms in PsA including (i) cell migration, invasion and cytokine expression (ii) phosphodiesterase signalling, and (iii) synovial angiogenesis and metabolism. These miRNA are significantly decreased in PsA synovial tissue and are associated with higher disease activity, synovial inflammation and erosive disease. Deficiency of these miRNA can induce PsA SFC migration, invasion and enhance pro-inflammatory cytokine production. We have identified several novel targets for these miRNAs which are known to be increased in PsA synovial tissue compared to osteoarthritis. Currently, using Crisper/Cas9 miRNA- loss-of-function studies in in vitro/in-vivo models we are examining the functional downstream effect which include angiogenesis, inflammatory signalling pathways and metabolism.