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Logo of arthrestherBioMed Centralbiomed central web sitesearchsubmit a manuscriptregisterthis articleArthritis Research & Therapy
 
Arthritis Res Ther. 2006; 8(2): R54.
Published online 2006 March 6. doi:  10.1186/ar1915
PMCID: PMC1526601

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

Abstract

Bone marrow CD34+ cells from rheumatoid arthritis (RA) patients have abnormal capacities to respond to tumor necrosis factor (TNF)-α and to differentiate into fibroblast-like cells producing matrix metalloproteinase (MMP)-1. We explored the expression of mRNA for nuclear factor (NF)κB in RA bone marrow CD34+ cells to delineate the mechanism for their abnormal responses to TNF-α. CD34+ cells were purified from bone marrow samples obtained from 49 RA patients and 31 osteoarthritis (OA) patients during joint operations via aspiration from the iliac crest. The mRNAs for NFκB1 (p50), NFκB2 (p52) and RelA (p65) were examined by quantitative RT-PCR. The expression of NFκB1 mRNA in bone marrow CD34+ cells was significantly higher in RA than in OA, whereas there was no significant difference in the expression of mRNA for NFκB2 and RelA. The expression of NFκB1 mRNA was not correlated with serum C-reactive protein or with the treatment with methotrexate or oral steroid. Silencing of NFκB1 by small interfering RNA abrogated the capacity of RA bone marrow CD34+ cells to differentiate into fibroblast-like cells and to produce MMP-1 and vascular endothelial growth factor upon stimulation with stem cell factor, granulocyte-macrophage colony stimulating factor and TNF-α without influencing their viability and capacity to produce β2-microglobulin. These results indicate that the enhanced expression of NFκB1 mRNA in bone marrow CD34+ cells plays a pivotal role in their abnormal responses to TNF-α and, thus, in the pathogenesis of RA.


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