Abstract
Rheumatoid arthritis (RA) is characterized by hyperplasia of synovial lining cells, consisting of macrophagelike type A synoviocytes and fibroblast-like type B synoviocytes. Type A synoviocytes, also called intimal macrophages, have been found to be derived from monocyte precursors in the bone marrow. Accordingly, the spontaneous generation of CD14+ cells from bone marrow CD14- progenitor cells is accelerated in RA, resulting in the facilitated entry of such CD14+ cells into the synovium. Whereas type B synoviocytes, also called fibroblast-like synoviocytes, are thought to arise from the sublining tissue or other support structures of the joint, they might be also derived from bone marrow progenitor cells. Thus, RA bone marrow CD34+ cells show abnormal responses to TNF-β , resulting in their accelerated differentiation into fibroblast-like cells producing MMP-1. On the other hand, persistent neovascularization is crucial for continuous synovial proliferation through delivery of nutrients and recruitment of inflammatory cells. In this regard, RA bone marrow CD34+ cells differentiate into endothelial cells much more effectively than control subjects, suggesting that bone marrow CD34+ cells might play a role in the synovial hyperplasia in RA through mobilization of endothelial progenitor cells that contribute to vasculogenesis. Taken together, these results support the hypothesis that the bone marrow, rather than the synovium, might be the primary-lesion site of RA.
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