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.
Highlights
Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by persistent synovial proliferation
We previously demonstrated that bone marrow CD34+ cells from RA patients have abnormal capacities to respond to tumor necrosis factor-α (TNF-α) and to differentiate into fibroblast-like cells (FLC) producing MMP-1, suggesting that bone marrow CD34+ cells might generate type B synoviocytes and could play an important role in the pathogenesis of RA (Hirohata et al.,2001)
3.3 Capacity of bone marrow dendritis cells (DC) to differentiate into type B synoviocytes We have recently demonstrated that bone marrow plasmacytoid DC as well as myeloid DC, irrespective of their origin from RA bone marrow or osteoarthritis (OA) bone marrow, have prominent capacity to differentiate into FLC producing MMP-1 especially under influences of TNF-α (Hirohata et al.,2011)
Summary
Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by persistent synovial proliferation. It should be pointed out that the expression of a variety of chemokines and adhesion molecules is enhanced in vascular endothelium and fibroblast-like synoviocytes in the RA synovium (Oppenheimer-Marks & Lipsky,1998; Patel et al.,2001; Kanbe et al.,2002 ), possibly facilitating the entry of such CD14+ CD16+ blood monocytes into the synovium These observations strongly support the hypothesis that the accelerated generation of CD14+ cells from bone marrow progenitor cells and the accelerated maturation of such CD14+ cells into tissue-infiltrative CD16+ monocytes before entry into the joint might play an important role in the pathogenesis of RA. Proliferative synovial tissues usually disappear at the site of bony ankylosis and total immobility These observations strongly support the hypothesis that the accelerated generation and continuous recruitment of bone marrowderived cells might play a critical role in the synovial hyperplasia in RA, accounting for the discrepancy between the marked synovial hyperplasia and the lack of evidence for accelerated proliferation of synoviocytes
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