Identification of key regulators for the migration and invasion of rheumatoid synoviocytes through a systems approach.

摘要: Rheumatoid synoviocytes, which consist of fibroblast-like synoviocytes (FLSs) and synovial macrophages (SMs), are crucial for the progression rheumatoid arthritis (RA). Particularly, FLSs RA patients (RA-FLSs) exhibit invasive characteristics reminiscent cancer cells, destroying cartilage bone. RA-FLSs SMs originate differently from mesenchymal myeloid respectively, but share many pathologic functions. However, molecular signatures biological networks representing distinct shared features two cell types unknown. We performed global transcriptome profiling obtained osteoarthritis patients. By comparing transcriptomes, we identified cellular processes defining invasiveness proinflammatory properties RA-SMs, respectively. Interestingly, under interleukin-1β (IL-1β)–stimulated condition, newly acquired signature dominant in RA-SMs without losing properties. next reconstructed a network model that delineates shared, RA-FLS–dominant (invasive), RA-SM–dominant (inflammatory) processes. From model, selected 13 genes, including periostin, osteoblast-specific factor (POSTN) twist basic helix–loop–helix transcription 1 (TWIST1), as key regulator candidates responsible FLS invasiveness. Of note, POSTN TWIST1 expressions were elevated independent further instigated by IL-1β. Functional assays demonstrated requirement migration invasion stimulated with Together, our systems approach to synovitis provides basis identifying regulators pathological -SMs, demonstrating how certain type cells acquires functional redundancy chronic inflammatory conditions.