Glucocorticoids induce the differentiation of a mesenchymal progenitor cell line, ROB-C26 into adipocytes and osteoblasts, but fail to induce terminal osteoblast differentiation
Glucocorticoids induce the differentiation of a mesenchymal progenitor cell line, ROB-C26 into adipocytes and osteoblasts, but fail to induce terminal osteoblast differentiation
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DOI：
10.1016/j.bone.2006.07.012
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发表时间：
2007-01-01
期刊：
影响因子：
4.1
通讯作者：
Takagi, Minoru
中科院分区：
文献类型：
--
作者：
Ito, Shinsuke;Suzuki, Naoto;Takagi, Minoru
为了阐明糖皮质激素（GCs）对成骨细胞和脂肪细胞分化的影响，我们研究了地塞米松（Dex），一种GC类似物对成骨细胞（Runx2， Dlx5和Osterix）和脂肪细胞（C/EBP，如C/EBP α， C/EB β和C/EBP δ， PPAR γ 2），晚期成骨细胞标志物，骨涎蛋白（BSP）和骨钙素（OC），以及脂肪细胞分化依赖蛋白aP2在克隆间充质祖细胞系中的影响。ROB-C26 (C26)。Dex对C26细胞具有剂量依赖性和时间依赖性，不仅增加了C/ ebp、PPAR γ 2和aP2的mRNA和蛋白表达，还增加了Runx2、Dlx5、BSP和OC的表达，但不诱导Osterix，认为其主要作用于终末成骨细胞分化。环己亚胺预处理表明，Dex信号立即增加C/ ebp和Dlx5的表达，而其余基因的表达需要从头合成蛋白质。连续的Dex处理刺激了脂肪细胞的形成，但未能诱导Osterix的表达和矿化基质的形成。然而，BMP-2处理dexx处理的细胞诱导Osterix表达和随后的矿化基质堡垒。上述结果表明，Dex上调C26细胞C/ ebp，上调PPAR γ 2和aP2表达，诱导脂肪细胞分化；Dex上调Dlx5，上调Runx2、BSP和OC表达，在基因和蛋白水平上上调Runx2、BSP和OC表达，但不能诱导Osterix表达，提示Dex不促进C26细胞终末成骨细胞分化。(c) 2006爱思唯尔公司版权所有。
To clarify the effects of glucocorticoids (GCs) on osteoblast and adipocyte differentiation, we investigated the effects of dexamethasone (Dex), a GC analogue on transcription factors for osteoblasts (Runx2, Dlx5 and Osterix) and adipocytes (C/EBPs such as C/EBP alpha, C/EB beta and C/EBP delta, and PPAR gamma 2), late osteoblastic markers, bone sialoprotein (BSP) and osteocalcin (OC), and adipocyte differentiation-dependent protein, aP2 in a clonal mesenchymal progenitor cell line, ROB-C26 (C26). C26 cells were dose- and time-dependently responsive to Dex in terms of an increase in not only mRNA and protein expressions of the C/EBPs, PPAR gamma 2 and aP2, but also Runx2, Dlx5, BSP and OC with no induction of Osterix, which is considered to act mainly on terminal osteoblast differentiation. Cycloheximide pretreatment indicated that Dex signaling immediately increases expressions of the C/EBPs and Dlx5, while expressions of the rest of the genes require de novo protein synthesis. Continuous Dex treatment stimulated adipocyte formation, but failed to induce Osterix expression and mineralized matrix formation. However, BMP-2 treatment of Dex-treated cells induced Osterix expression and subsequent mineralized matrix fort-nation. These results indicate that Dex up-regulates the C/EBPs followed by increasing PPAR gamma 2 and aP2 expressions in C26 cells to induce adipocyte differentiation, while Dex enhances Dlx5 followed by increasing Runx2, BSP and OC expressions at gene and protein levels, but cannot induce Osterix expression, suggesting that Dex does not promote their terminal osteoblast differentiation. (c) 2006 Elsevier Inc. All rights reserved.