%0 Journal Article
%T Enhanced expression of mRNA for nuclear factor 百B1 (p50) in CD34+ cells of the bone marrow in rheumatoid arthritis
%A Shunsei Hirohata
%A Yasushi Miura
%A Tetsuya Tomita
%A Hideki Yoshikawa
%A Takahiro Ochi
%A Nicholas Chiorazzi
%J Arthritis Research & Therapy
%D 2006
%I BioMed Central
%R 10.1186/ar1915
%X 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)-汐 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-汐 is one of the first triggers to be found effective for the activation of nuclear factor (NF)百B 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-汐 blockade has beneficial effects in the treatment of RA [4]. Moreover, inhibition of NF百B by the antioxidant N-acetylcysteine significantly reduced TNF-汐- and NF百B-dependent gene expression and synovial proliferation [3]. We thus hypothesized that abnormal responses of RA bone marrow CD34+ cells to TNF-汐 might result from abnormal expression of NF百B genes. The current studies were undertaken, therefore, to explore the expression of mRNA for various components of NF百B in bone marrow CD34+ cells in RA.Bone marrow samples
%U http://arthritis-research.com/content/8/2/R54