Identification of microRNAs association with Rheumatoid Arthritis Synovial Fibroblasts using the Human TNF Transgenic Mouse Model

OBJECTIVE: MicroRNAs (miRNAs, miRs), a class of small non-coding RNA molecules, are posttranscriptional regulators involved in a plethora of cellular functions and have been proposed as potential therapeutic targets in various diseases, including rheumatoid arthritis (RA). In this study, we sought to discover novel miR associations in synovial fibroblasts (SFs), a key cell type mediating RA pathogenesis, by performing miR expression profiling on cells isolated from the human TNF transgenic mouse model (TghuTNF or Tg197). METHODS: miR expression in SFs isolated from 8-week-old, fully diseased TghuTNF and WT littermate control mice were determined by deep sequencing of small RNAs and the arthritic profile was established by pairwise comparisons of the two groups. qRT-PCR analysis was utilised for profile validation purposes and miR quantitation in patient SFs. Dysregulated miR target genes and pathways were predicted via bioinformatic algorithms. Overall design: Synovial Fibroblasts isolated from TghuTNF mice (2 x biological replicates) and control WT littermate mice (2 x biological replicates)

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Pandis I, Ospelt C, Karagianni N, Denis MC, Reczko M, Camps C, Hatzigeorgiou AG, Ragoussis J, Gay S, Kollias G