Session Title: Rheumatoid Arthritis: Human Etiology and Pathogenesis II
Session Type: Abstract Submissions (ACR)
Background/Purpose: We previously showed that bone marrow (BM) CD34+ cells from rheumatoid arthritis (RA) patients have abnormal capacities to respond to tumor necrosis factor alpha and to differentiate into fibroblast-like cells producing MMP-1, resembling type B synoviocyte. In addition, we have recently demonstrated that the mRNA expression of nuclear factor kappa B1 (NFkB1) (p50), Krüppel-like factor 5 (KLF-5) and FK506-binding protein 5 (FKBP5) in BM CD34+ cells is significantly higher in RA patients than osteoarthritis (OA) patients. Triggering receptor expressed on myeloid cells 1 (TREM-1) is a recently identified cell surface receptor that is inducible mainly on monocytes and neutrophils, and plays an important role as amplifier of inflammatory response in acute and chronic inflammatory conditions. Recent studies have disclosed increased TREM-1 expression in rheumatoid synovial tissue, and have suggested that TREM-1 ligation contributes to the pathogenesis of RA. The current study therefore examined the mRNA expression of TREM-1 in BM CD34+ cells from RA patients.
Methods: BM samples were obtained from 48 patients with RA (6 males and 42 females: mean age 58.8 years) and 30 patients with OA (3 males and 27 females: mean age 71.1 years), who gave informed consent, during joint operations via aspiration from iliac crest. CD34+ cells were purified from the BM mononuclear cells by positive selection with magnetic beads. The expression of mRNA for TREM-1 was examined by quantitative reverse transcription PCR and is shown as the ratio of the copy numbers to those of beta-actin mRNA.
Results: The expression of mRNA for TREM-1 was significantly higher in RA BM CD34+ cells than OA BM CD34+ cells (Fig. A). The TREM-1 mRNA expression level was not correlated with serum C-reactive protein or with the administration of methotrexate or oral steroid (Fig. B). TREM-1 mRNA expression was significantly correlated with NFkB1 (r=0.56, p<0.0001), KLF-5 (r=0.75, p<0.0001) and FKBP5 (r=0.62, p<0.0001) mRNA expression in RA BM CD34+ cells.
Conclusion: These results indicate that the enhanced expression of TREM-1 mRNA in BM CD34+ cells plays a pivotal role in the pathogenesis of RA, and might be secondary to the enhanced mRNA expression of NFkB1, KLF-5 or FKBP5.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/enhanced-expression-of-mrna-for-triggering-receptor-expressed-on-myeloid-cells-1-in-cd34-cells-of-the-bone-marrow-in-rheumatoid-arthritis/