Local fibroblast proliferation but not influx is responsible for synovial hyperplasia in a murine model of rheumatoid arthritis.
Local fibroblast proliferation but not influx is responsible for synovial hyperplasia in a murine model of rheumatoid arthritis.
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在类风湿关节炎小鼠模型中，局部成纤维细胞增殖而不是流入是导致滑膜增生的原因。
DOI：
10.1016/j.bbrc.2016.01.121
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发表时间：
2016
期刊：
影响因子：
--
通讯作者：
and Hitoshi Kohsaka
中科院分区：
文献类型：
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作者：
Yusuke Matsuo;Fumitaka Mizoguchi;Tetsuya Saito;Kimito Kawahata;Satoshi Ueha;Kouji Matsushima;Yutaka Inagaki;Nobuyuki Miyasaka;and Hitoshi Kohsaka
滑膜成纤维细胞在类风湿性关节炎（RA）的炎症和关节破坏中起着至关重要的作用。它们如何在RA关节中积累仍不清楚。进行本研究以辨别来自关节外部的细胞流入和局部增殖是否是RA动物模型中滑膜成纤维细胞积聚的原因。我们发现，滑膜成纤维细胞被确定为GFP+细胞使用胶原蛋白I型α 2（Col 1a 2）-GFP转基因报告小鼠。然后，利用骨髓移植和联体共生技术研究细胞内流。将来自Col 1a 2-GFP小鼠的骨髓移植到经辐照的野生型小鼠。将Col 1a 2-GFP和野生型小鼠结合用于联体生活。移植小鼠和寄生虫进行胶原抗体诱导的关节炎（CAIA）。我们在CAIA移植小鼠和CAIA野生型寄生虫的增生性滑膜组织中没有发现GFP+细胞。此外，研究了Col 1a 2-GFP小鼠和基于荧光泛素化的细胞周期指示剂（Fucci）转基因小鼠的正常和CAIA滑膜组织（其中细胞周期的S/G2/M期的细胞表达Azami-Green）的Ki 67（细胞增殖标记物）和波形蛋白（成纤维细胞标记物）表达。CAIA滑膜组织中Ki 67 +/GFP+和Azami-Green+/vimentin+细胞的百分比高于未处理的滑膜组织中的百分比（分别为34%对0.40%和19%对0.26%）。这些结果表明，局部成纤维细胞增殖，而不是细胞内流是负责在CAIA滑膜增生。抑制局部滑膜成纤维细胞的增殖应该是治疗RA的一种有希望的方法。
Synovial fibroblasts play crucial roles in inflammation and joint destruction in rheumatoid arthritis (RA). How they accumulate in the RA joints remains unclear. This study was conducted to discern whether cellular influx from the outside of the joints and local proliferation are responsible for synovial fibroblast accumulation in an animal model of RA. We found that synovial fibroblasts were identified as GFP+ cells using collagen type I alpha 2 (Col1a2)-GFP transgenic reporter mice. Then, bone marrow transplantation and parabiosis techniques were utilized to study the cellular influx. Irradiated wild-type mice were transplanted with bone marrow from Col1a2-GFP mice. Col1a2-GFP and wild-type mice were conjoined for parabiosis. The transplanted mice and the parabionts were subjected to collagen antibody-induced arthritis (CAIA). We found no GFP+ cells in the hyperplastic synovial tissues from the transplanted mice with CAIA and from the wild-type parabionts with CAIA. Furthermore, normal and CAIA synovial tissues from Col1a2-GFP mice and from fluorescent ubiquitination-based cell cycle indicator (Fucci) transgenic mice, in which cells in S/G2/M phases of the cell cycle express Azami-Green, were studied for Ki67, a cellular proliferation marker, and vimentin, a fibroblast marker, expression. The percentages of Ki67+/GFP+ and Azami-Green+/vimentin+ cells in the CAIA synovial tissues were higher than those in the untreated synovial tissues (34% vs. 0.40% and 19% vs. 0.26%, respectively). These findings indicate that local fibroblast proliferation but not cellular influx is responsible for the synovial hyperplasia in CAIA. Suppression of proliferation of the local synovial fibroblasts should be a promising treatment for RA.