Enhanced expression of mRNA for nuclear factor κB1 (p50) in CD34+ cells of the bone marrow in rheumatoid arthritis

Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by hyperplasia of synovial lining cells, consisting of macrophage-like type A synoviocytes and fibroblast-like type B synoviocytes [1]. It has been appreciated that type A synoviocytes, which are also called intimal macrophages, are derived from monocyte precursors in the bone marrow [1]. On the other hand, type B synoviocytes, which are also called fibroblast-like synoviocytes, have the morphological appearance of fibroblasts as well as the capacity to produce and secrete a variety of factors, including proteoglycans, cytokines, arachidonic acid metabolites, and matrix metalloproteinases (MMPs), that lead to the destruction of joints [1]. Apart from type A synoviocytes, the origin of type B synoviocytes has been unclear [1]. Of note, we have recently demonstrated that bone marrow CD34+ cells from RA patients have abnormal capacities to respond to tumor necrosis factor (TNF)-α and to differentiate into fibroblast-like cells producing MMP-1, suggesting that bone marrow CD34+ progenitor cells might generate type B synoviocytes and thus could play an important role in the pathogenesis of RA [2].TNF-α is one of the first triggers to be found effective for the activation of nuclear factor (NF)κB in RA synovium [3]. This mechanism of activation was followed by up-regulation of several inflammatory genes usually found in active RA. Accordingly, a number of studies have shown that TNF-α blockade has beneficial effects in the treatment of RA [4]. Moreover, inhibition of NFκB by the antioxidant N-acetylcysteine significantly reduced TNF-α- and NFκB-dependent gene expression and synovial proliferation [3]. We thus hypothesized that abnormal responses of RA bone marrow CD34+ cells to TNF-α might result from abnormal expression of NFκB genes. The current studies were undertaken, therefore, to explore the expression of mRNA for various components of NFκB in bone marrow CD34+ cells in RA.Bone marrow samples