Interleukin-6 inhibits early differentiation of ATDC5 chondrogenic progenitor cells
Interleukin-6 inhibits early differentiation of ATDC5 chondrogenic progenitor cells
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DOI：
10.1016/j.cyto.2009.05.002
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发表时间：
2009-08-01
期刊：
影响因子：
3.8
通讯作者：
Yokota, Shumpei
中科院分区：
文献类型：
--
作者：
Nakajima, Shoko;Naruto, Takuya;Yokota, Shumpei
白细胞介素（IL）-6是全身性幼年特发性关节炎（sJIA）的病原体，sJIA是一种伴有严重生长障碍的慢性炎症性疾病。最近的抗IL-6受体单克隆抗体tocilizumab的试验表明，tocilizumab阻断IL-6/IL-6受体介导的炎症，并诱导sJIA儿童的追赶性生长。本研究评估了IL-6对ATDC 5细胞软骨形成的影响，ATDC 5细胞是一种克隆小鼠软骨形成细胞系，为研究生长板内软骨骨化提供了一个很好的模型。用荧光激活细胞分选分析法检测ATDC 5细胞IL-6受体和gp 130的表达。将重组鼠IL-6加入到ATDC 5培养物中以观察细胞分化，使用软骨形成分化标志物II型胶原、聚集蛋白聚糖和X型胶原的定量RT-PCR。为了阻断IL-6，加入抗小鼠IL-6受体单克隆抗体MR 16 -1。结果，细胞表达IL-6受体和gp 130。软骨分化标志基因的表达被IL-6降低，但这被MR 16 -1废除。我们的结论是，IL-6抑制ATDC 5细胞的早期软骨形成，这表明IL-6可能会影响在细胞水平上的定向干细胞在软骨分化的生长板软骨细胞，IL-6可能是一个细胞水平的因素在sJIA的生长障碍。(C)2009爱思唯尔有限公司保留所有权利。
Interleukin (IL)-6 is a causative agent of systemic juvenile idiopathic arthritis (sJIA), a chronic inflammatory disease complicated with severe growth impairment. Recent trials of anti-IL-6 receptor monoclonal antibody, tocilizumab, indicated that tocilizumab blocks IL-6/IL-6 receptor-mediated inflammation, and induces catch-up growth in children with sJIA. This study evaluates the effects of IL-6 on chondrogenesis by ATDC5 cells, a clonal murine chondrogenic cell line that provides an excellent model for studying endochondral ossification at growth plate. ATDC5 cells were examined for the expression of IL-6 receptor and gp130 by fluorescence-activated cell sorting analysis. Recombinant murine IL-6 was added to ATDC5 cultures to observe cell differentiation, using a quantitative RT-PCR for the chondrogenic differentiation markers type II collagen, aggrecan, and type X collagen. To block IL-6, the anti-mouse IL-6 receptor monoclonal antibody MR16-1 was added. As a result, the cells expressed IL-6 receptor and gp130. The expression of chondrogenic differentiation marker gene was reduced by IL-6, but this was abrogated by MR16-1. We conclude that IL-6 inhibits early chondrogenesis of ATDC5 cells suggesting that IL-6 may affect committed stem cells at a cellular level during chondrogenic differentiation of growth plate chondrocytes, and that IL-6 may be a cellular-level factor in growth impairment in sJIA. (C) 2009 Elsevier Ltd. All rights reserved.