Elucidating bone marrow edema and myelopoiesis in murine arthritis using contrast-enhanced magnetic resonance imaging.

Elucidating bone marrow edema and myelopoiesis in murine arthritis using contrast-enhanced magnetic resonance imaging.
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使用对比度增强的磁共振成像阐明鼠关节炎中骨髓水肿和骨髓病。

DOI:
10.1002/art.23546
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发表时间:
2008-07
影响因子:
--
通讯作者:
Schwarz, Edward M.
Schwarz, Edward M.
中科院分区:
其他
文献类型:
--
作者:
Proulx, Steven T.;Kwok, Edmund;You, Zhigang;Papuga, M. Owen;Beck, Christopher A.;Shealy, David J.;Calvi, Laura M.;Ritchlin, Christopher T.;Awad, Hani A.;Boyce, Brendan F.;Xing, Lianping;Schwarz, Edward M.

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虽然通过磁共振成像(MRI)检测到的骨髓水肿(BME)是关节炎的生物标志物,但由于临床研究的局限性,其性质仍然知之甚少。在这项研究中,MRI的小鼠关节炎是用来阐明其细胞组成和血管参与。使用对比前MRI的标准化骨髓强度(NBMI)和静脉注射钆喷酸葡胺后的标准化骨髓对比增强(NMCE)定量BME。野生型(WT)和肿瘤坏死因子(TNF)转基因小鼠进行扫描,从2至5个月的年龄,然后进行骨髓的组织学或荧光激活细胞分选(FACS)分析。在疗效研究中,TNF转基因小鼠用抗TNF或安慰剂治疗8周,然后使用每两个月一次的MRI和组织学分析进行研究。在2个月时,WT和TNF转基因小鼠的NBMI值相似。此后,WT小鼠的值稳定下降,平均值在3.5个月时与TNF转基因小鼠的值显著不同(平均值± SD 0.29 ± 0.08 vs 0.46 ± 0.13; P < 0.05)。如在5个月时的组织学观察,WT而非TNF转基因小鼠中发生了红骨髓向黄骨髓的转化。接受抗TNF治疗的TNF转基因小鼠的骨髓转化为黄色骨髓,6周时NBMI值低于安慰剂组(平均值± SD 0.26 ± 0.07 vs 0.61 ± 0.22; P < 0.05)。骨髓流式细胞术分析显示NBMI值与CD 11b+单核细胞之间存在显著相关性(R2 = 0.91,P = 0.0028)。建立了“正常”红骨髓与病理性BME的对比,还发现炎症骨髓对造影剂具有高度渗透性。TNF转基因小鼠中的BME信号是由黄骨髓向红骨髓转化引起的,骨髓生成增加,骨髓渗透性增加。调节这些变化的因素值得进一步研究。
While bone marrow edema (BME) detected by magnetic resonance imaging (MRI) is a biomarker of arthritis, its nature remains poorly understood due to the limitations of clinical studies. In this study, MRI of murine arthritis was used to elucidate its cellular composition and vascular involvement. BME was quantified using normalized bone marrow intensity (NBMI) from precontrast MRI and normalized marrow contrast enhancement (NMCE) following intravenous administration of gadopentate dimeglumine. Wild-type (WT) and tumor necrosis factor (TNF)-transgenic mice were scanned from 2 to 5 months of age, followed by histologic or fluorescence-activated cell sorting (FACS) analysis of marrow. In efficacy studies, TNF-transgenic mice were treated with anti-TNF or placebo for 8 weeks, and then were studied using bimonthly MRI and histologic analysis. NBMI values were similar in WT and TNF-transgenic mice at 2 months. The values in WT mice steadily decreased thereafter, with mean values becoming significantly different from those of TNF-transgenic mice at 3.5 months (mean ± SD 0.29 ± 0.08 versus 0.46 ± 0.13; P < 0.05). Red to yellow marrow transformation occurred in WT but not TNF-transgenic mice, as observed histologically at 5 months. The marrow of TNF-transgenic mice that received anti-TNF therapy converted to yellow marrow, with lower NBMI values versus placebo at 6 weeks (mean ± SD 0.26 ± 0.07 versus 0.61 ± 0.22; P < 0.05). FACS analysis of bone marrow revealed a significant correlation between NBMI values and CD11b+ monocytes (R2 = 0.91, P = 0.0028). Thresholds for “normal” red marrow versus pathologic BME were established, and it was also found that inflammatory marrow is highly permeable to contrast agent. BME signals in TNF-transgenic mice are caused by yellow to red marrow conversion, with increased myelopoiesis and increased marrow permeability. The factors that mediate these changes warrant further investigation.
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影响因子: 27.4
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发表时间: 2003-08-01
期刊: SPRINGER SEMINARS IN IMMUNOPATHOLOGY
影响因子: --
作者:
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