Enhanced expression of mRNA for FK506-binding protein 5 in bone marrow CD34 positive cells in patients with rheumatoid arthritis.
Enhanced expression of mRNA for FK506-binding protein 5 in bone marrow CD34 positive cells in patients with rheumatoid arthritis.
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DOI：
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发表时间：
2010
影响因子：
3.7
通讯作者：
R. Matsushita;A. Hashimoto;T. Tomita;H. Yoshitawa;S. Tanaka;H. Endo;S. Hirohata
中科院分区：
文献类型：
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作者：
R. Matsushita;A. Hashimoto;T. Tomita;H. Yoshitawa;S. Tanaka;H. Endo;S. Hirohata
目的研究发现类风湿关节炎（RA）患者骨髓单个核细胞中多个基因表达上调。然而，目前还不清楚这种异常是由全身炎症还是干细胞水平的异常引起的。因此，目前的研究检查了几个代表性基因的表达，包括双调蛋白（AREG），趋化因子受体4（CXCR 4）和FK 506结合蛋白5（FKBP 5）在RA BM CD 34+细胞中。方法取52例RA和35例OA患者关节手术中的骨髓标本。通过用磁珠阳性选择从BM单核细胞中纯化CD 34+细胞。使用定量实时PCR测量AREG、CXCR 4和FKBP 5的mRNA表达。结果RA BM CD 34+细胞中FKBP 5 mRNA的表达显著高于OA BM CD 34+细胞，而AREG和CXCR 4 mRNA的表达则无显著差异。FKBP 5 mRNA表达水平与血清CRP及治疗无关。此外，肿瘤坏死因子-α没有增强健康供体BM CD 34+细胞中FKBP 5 mRNA的表达。结论FKBP 5在骨髓CD 34+细胞中的表达增强可能是RA骨髓CD 34+细胞的一种内在异常，而AREG和CXCR 4在骨髓单个核细胞中的表达增强可能是继发于全身炎症的。
OBJECTIVE Recent studies have disclosed that several genes are up-regulated in bone marrow (BM) mononuclear cells from rheumatoid arthritis (RA) patients. However, it remains unclear whether such abnormalities result from systemic inflammation or from abnormalities at stem cell level. The current study therefore examined the expression of several representative genes, including amphiregulin (AREG), chemokine receptor 4 (CXCR4), and FK506-binding protein 5 (FKBP5) in RA BM CD34+ cells. METHODS BM samples were obtained from 52 patients with RA and 35 patients with osteroarthritis (OA) during joint operations. CD34+ cells were purified from the BM mononuclear cells by positive selection with magnetic beads. The mRNA expression for AREG, CXCR4, and FKBP5 was measured using quantitative real-time PCR. RESULTS The expression of mRNA for FKBP5, but not that of AREG or CXCR4, was significantly higher in RA BM CD34+ cells than in OA BM CD34+ cells. The FKBP5 mRNA expression level was not correlated with serum CRP or treatment. In addition, tumour necrosis factor-alpha did not enhance the expression of FKBP5 mRNA in BM CD34+ cells from healthy donors. CONCLUSION The results suggest that the enhanced expression of FKBP5 in BM CD34+ cells might be an intrinsic abnormality of RA BM CD34+ cells, whereas the enhanced expression of AREG and CXCR4 in BM mononuclear cells might be secondary to systemic inflammation.