Fibroblasts andFibroblast-like Synoviocytes

Recent advances in single-cell transcriptomic analysis have demonstrated unexpected diversity of fibroblast phenotypes within the synovium during embryogenesis, adulthood, and disease, with discrete markers and functions, offering dramatic new understanding of disease mechanisms and the potential to transform therapeutic approaches to disease. Fibroblasts are programmed epigenetically to determine the unique structure and function of different organs and tissues. However, these unique features might contribute to organ-specific disease. Tissue fibroblasts may be recruited from a number of sources and cell types including the bone marrow, blood, and local stromal cells and act as organ-specific innate immune sentinel cells. Under inflammatory conditions, fibroblasts become key immune system players by recruiting and modulating the behavior and survival of infiltrating immune cells. Fibroblasts can be programmed epigenetically through exposure to inflammatory and environmental stress such that they inappropriately prolong inflammation, which becomes persistent. Within the synovium, persistent abnormal behavior of fibroblasts results in continued damage to vital joint structures such as cartilage and bone, which, if untreated, will result in deformity and functional impairment.