Osteoblast differentiation of NIH3T3 fibroblasts is associated with changes in the IGF-I/IGFBP expression pattern.
Osteoblast differentiation of NIH3T3 fibroblasts is associated with changes in the IGF-I/IGFBP expression pattern.
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DOI：
10.2478/s11658-006-0038-y
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发表时间：
2006
影响因子：
8.3
通讯作者：
Abdallah BM
中科院分区：
文献类型：
--
作者：
Abdallah BM
胰岛素样生长因子（IGFs）和胰岛素样生长因子结合蛋白（IGFBPs）是成骨细胞增殖和分化的重要调节因子。据报道，地塞米松（Dex），一种活性糖皮质激素（GC）类似物，协同1，25-二羟维生素D3（1，25（OH）2D 3）对小鼠成纤维细胞系NIH 3 T3中成骨细胞分化的刺激作用。我调查了这种刺激作用是否与IGF/IGFBP系统表达模式的变化有关。定量实时PCR技术被用来量化IGF-系统的基因表达水平在成骨细胞分化过程中，并在含血清和无血清培养条件下，单独响应于1，25（OH）2D 3或Dex。有趣的是，NIH 3 T3显示出表达高水平的IGF-I、IGF-II和IGFBP-5的mRNA，以及低水平的IGFBP-2和IGFBP-6。在成骨细胞分化期间（第6-12天），IGF-I mRNA被抑制超过60%，而IGFBP-5的转录物被显著上调超过50倍。同样地，单独用Dex治疗导致IGFBP-5表达的剂量和时间依赖性增加和IGF-I mRNA的减少。单独用1，25（OH）2D 3处理可使IGF-I和IGFBP-6的mRNA水平分别增加约4倍和7倍，并呈剂量和时间依赖性。总之，我的数据表明，NIH 3 T3的成骨细胞分化与IGFs/IGFBPs表达模式的变化有关，IGFs/IGFBPs在1，25（OH）2D 3存在下受糖皮质激素调节。糖皮质激素对IGF/IGFBP水平的调节可能表明IGF系统在介导NIH 3 T3细胞系的成骨细胞分化中起重要作用。
Insulin-like growth factors (IGFs) and IGF-binding proteins (IGFBPs) are essential regulators for osteoblast proliferation and differentiation. It has been reported that Dexamethasone (Dex), an active glucocorticoid (GC) analogue, synergizes the stimulatory effect of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) on osteoblast differentiation in the mouse fibroblastic cell line NIH3T3. I investigated whether this stimulatory effect is associated with changes in the expression pattern of the IGF/IGFBP system. Quantitative real-time PCR technology was used to quantify the gene expression levels of the IGF-system during osteoblast differentiation and in response to 1,25(OH)2D3 or Dex alone under serum-containing and serum-free culture conditions. Interestingly, NIH3T3 was shown to express high mRNA levels of IGF-I, IGF-II and IGFBP-5, and low levels of both IGFBP-2 and-6. During osteoblast differentiation (days 6-12), IGF-I mRNA was repressed by more than 60%, while the transcript of IGFBP-5 was markedly up-regulated, by more than 50-fold. Similarly, treatment with Dex alone resulted in a dose-and time-dependent increase in the expression of IGFBP-5 and a decrease in IGF-I mRNA. Treatment with 1,25(OH)2D3 alone increased the mRNA levels of IGF-I and IGFBP-6 by around 4-and 7-fold, respectively, in a dose-and time-dependent manner. In conclusion, my data demonstrated that osteoblast differentiation of NIH3T3 is associated with changes in the expression pattern of IGFs/IGFBPs, which are regulated by glucocorticoid in the presence of 1,25(OH)2D3. Modulation of the IGF/IGFBP levels by glucocorticoid might suggest important roles for the IGF-system in mediating the osteoblast differentiation of the NIH3T3 cell line.
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影响因子：
4.1
作者：
Durant, D;Pereira, RMR;Canalis, E
通讯作者：
Canalis, E
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Canalis, E;Bilezikian, JP;Giustina, A
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Giustina, A
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Eijken, M;Koedam, M;van Leeuwen, JPTM
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van Leeuwen, JPTM