IL-6 receptor expression and IL-6 effects change during osteoblast differentiation

IL-6 receptor expression and IL-6 effects change during osteoblast differentiation
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DOI:
10.1016/j.cyto.2008.05.007
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发表时间:
2008-08-01
期刊:
影响因子:
3.8
通讯作者:
Lindgren, Urban
Lindgren, Urban
中科院分区:
医学3区
文献类型:
--
作者:
Li, Yan;Bakesjo, Carl-Magnus;Lindgren, Urban

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白细胞介素-6对成骨细胞的影响的研究产生了相互矛盾的结果。在几个早期的体外研究中,已经指出,除非加入可溶性IL-6受体,否则IL-6对成骨细胞没有影响。这些结果与IL-6受体在体内成骨细胞中表达的事实相矛盾。本研究将MC 3 T3前成骨细胞和大鼠骨髓基质细胞分别培养在含有抗坏血酸、磷酸甘油和地塞米松的成骨诱导培养基中。我们发现,IL-6受体的表达增加,在这两种类型的细胞在体外分化。此外,在MC 3 T3细胞中,IL-6以适当的顺序降低增殖并增强两种成骨细胞特异性分化标志物Runx 2和骨钙素的表达。有趣的是,在这两种细胞类型中,IL-6仅在培养后期诱导细胞凋亡。我们还发现,在MC 3 T3细胞中,IL-6诱导的STAT 3活化在培养后期显著更高,即当IL-6受体表达高时。目前的研究表明,IL-6受体表达增加,在体外成骨细胞分化和IL-6的功能作为前成骨细胞的分化调节剂和更成熟的细胞中的凋亡启动子。(c)2008爱思唯尔有限公司保留所有权利。
Studies of the effects of interleukin-6 on osteoblasts; have yielded conflicting results. In several earlier in vitro studies it has been stated that IL-6 has no effects on osteoblasts unless soluble IL-6 receptor is added. These results are contradictory to the fact that IL-6 receptors are expressed in osteoblasts in vivo. In this study, MC3T3 preosteoblast cells and rat bone marrow stromal cells were cultured in bone inducing medium containing ascorbic acid, p-glycerophosphate or dexamethasone. We found that IL-6 receptor expression increased in both types of cells during in vitro differentiation. Furthermore in MC3T3 cells IL-6 decreased proliferation and enhanced expression of two osteoblast-specific differentiation markers, Runx2 and osteocalcin, in proper sequential order. Interestingly, in both cell types IL-6-induced apoptosis only in later culture stages. We also found in MC3T3 cells that IL-6 induced STAT3 activation was significantly higher in later culture stages, i.e. when IL-6 receptor expression was high. The present study shows that IL-6 receptor expression increases during in vitro osteoblast differentiation and that IL-6 functions as a differentiation regulator of preosteoblast cells and an apoptosis initiator in more mature cells. (c) 2008 Elsevier Ltd. All rights reserved.