Species-specific glucocorticoid and 1,25-dihydroxyvitamin D responsiveness in mouse MC3T3-E1 osteoblasts: Dexamethasone inhibits osteoblast differentiation and vitamin D down-regulates osteocalcin gene expression
Species-specific glucocorticoid and 1,25-dihydroxyvitamin D responsiveness in mouse MC3T3-E1 osteoblasts: Dexamethasone inhibits osteoblast differentiation and vitamin D down-regulates osteocalcin gene expression
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DOI：
10.1210/en.138.5.2117
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发表时间：
1997-05-01
期刊：
影响因子：
4.8
通讯作者：
Stein, JL
中科院分区：
文献类型：
--
作者：
Lian, JB;Shalhoub, V;Stein, JL
小鼠MC 3 T3-E1细胞系是非致瘤性的，并且在体外经历成骨细胞分化的典型程序，产生骨样矿化细胞外基质。我们报告了这些细胞对地塞米松（Dex）和1，25-（OH）（2）D-3的反应，这与其他成骨细胞培养系统的结果相反。首先，在增殖期开始，将早期和晚期传代的MC 3 T3-E1细胞长期暴露于10（-7）M Dex，阻断了成骨细胞的分化，与在胎鼠颅骨衍生细胞培养物中观察到的分化增强相反。其次，1，25-（OH）（2）D-3不上调内源性小鼠骨钙素（OC）基因的表达（信使RNA或蛋白质合成）。几行的证据表明，这种反应是由小鼠OC维生素D反应元件的序列特异性。我们还观察到24小时类固醇激素处理后，矿化前和矿化后阶段成骨细胞之间细胞生长（组蛋白H2 B）和表型相关基因（胶原、OC、骨桥蛋白、糖皮质激素受体和1，25-（OH）（2）D-3受体）表达的定性和定量差异。我们在MC 3 T3-E1细胞中的发现与目前的概念一致，即1，25-（OH）（2）D-3和糖皮质激素作为成骨细胞成熟的功能的选择性影响。然而，10（-7）M的慢性Dex对成骨细胞分化的抑制和1，25-（OH）（2）D-3对OC的下调是与成骨细胞分化过程中小鼠骨表达基因对类固醇激素的物种特异性反应相关的新观察结果。
The mouse MC3T3-E1 cell line is nontumorigenic and undergoes a typical program of osteoblast differentiation in vitro, producing a bone-like mineralized extracellular matrix. We report responses of these cells to dexamethasone (Dex) and 1,25-(OH)(2)D-3 that are in contrast to findings from other osteoblast culture systems. First, chronic exposure of both early- and late-passaged MC3T3-E1 cells to 10(-7) M Dex, initiated during the proliferation period, blocked osteoblast differentiation, in contrast to the enhanced differentiation observed in cultures of fetal rat calvarial-derived cells. Secondly, 1,25-(OH)(2)D-3 did not up-regulate expression (messenger RNA or protein synthesis) of the endogenous mouse osteocalcin (OC) gene. Several lines of evidence are presented that suggest this response is caused by sequence specific properties of the mouse OC vitamin D response element. We also observed both qualitative and quantitative differences in expression of cell growth (histone H2B) and phenotype-related genes (collagen, OC, osteopontin, glucocorticoid receptor, and 1,25-(OH)(2)D-3 receptor), between pre- and postmineralization stage osteoblasts, in response to 24 h steroid hormone treatment. Our findings in MC3T3-E1 cells are consistent with current concepts of selective influences of 1,25-(OH)(2)D-3 and glucocorticoids as a function of osteoblast maturation. However, the inhibition of osteoblast differentiation by chronic Dex at 10(-7) M and the down-regulation of OC by 1,25-(OH)(2)D-3 are novel observations relevant to species-specific responsiveness of mouse bone-expressed genes to steroid hormones during osteoblast differentiation.