Enhanced expression of vascular endothelial growth factor in human SaOS-2 osteoblast-like cells and murine osteoblasts induced by insulin-like growth factor I.
Enhanced expression of vascular endothelial growth factor in human SaOS-2 osteoblast-like cells and murine osteoblasts induced by insulin-like growth factor I.
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DOI：
10.1210/endo.137.6.8641174
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发表时间：
1996-06
期刊：
影响因子：
4.8
通讯作者：
D. Goad;J. Rubin;Hong Wang;A. Tashjian;C. Patterson
中科院分区：
文献类型：
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作者：
D. Goad;J. Rubin;Hong Wang;A. Tashjian;C. Patterson
新毛细血管的形成是组织生长和修复的关键组成部分，是骨发育、形成和重塑过程中公认的过程。血管内皮生长因子 (VEGF) 是一种强效血管生成因子，对内皮细胞具有特定的促有丝分裂作用，由包括成骨细胞在内的许多细胞类型以调节方式产生。本研究的目的是检验胰岛素样生长因子 I (IGF-I)（一种已知的成骨因子）调节成骨细胞中 VEGF 表达的假设。在人 SaOS-2 成骨细胞样细胞中，10 nM IGF-I 在 2 小时时使 VEGF 信使 RNA (mRNA) 的丰度增加至对照值的 4 倍，并且 mRNA 的升高水平在 8 小时时恢复到接近基础值。 IGF-I 在 IGF-I 浓度低至 1-2 nM 时刺激 VEGF mRNA 水平。 IGF-I处理后VEGF mRNA的稳定性并未增加，放线菌素D消除了IGF-I增强的VEGF mRNA表达，表明IGF-I的作用可能是通过转录机制介导的。通过免疫印迹分析检测，SaOS-2 细胞中 IGF-I 诱导 VEGF mRNA 与免疫反应性 VEGF 蛋白的增加相关。 IGF-I 还增加了原代小鼠成骨细胞中 VEGF mRNA 的表达，这证实了 IGF-I 的作用并非 SaOS-2 细胞所独有。我们得出的结论是，IGF-I 增强 VEGF 的成骨细胞合成，然后 VEGF 可能局部作用于内皮，刺激血管生成，这是骨生长和重塑的重要组成部分。
Formation of new capillaries, a critical component of tissue growth and repair, is a recognized process in the development, formation, and remodeling of bone. Vascular endothelial growth factor (VEGF), a potent angiogenic factor with specific mitogenic actions on endothelial cells, is produced in a regulated manner by many cell types, including osteoblasts. The aim of the present investigation was to test the hypothesis that insulin-like growth factor I (IGF-I), a known osteogenic factor, modulates VEGF expression in osteoblasts. In human SaOS-2 osteoblast-like cells, 10 nM IGF-I increased the abundance of VEGF messenger RNA (mRNA) by 4-fold above the control value at 2h, and the elevated levels of mRNA returned to near basal by 8 h. IGF-I stimulated VEGF mRNA levels at IGF-I concentrations as low as 1-2 nM. The stability of VEGF mRNA was not increased after IGF-I treatment, and actinomycin D abrogated the enhanced expression of VEGF mRNA by IGF-I, indicating that the action of IGF-I was probably mediated by a transcriptional mechanism. The induction of VEGF mRNA by IGF-I in SaOS-2 cells was associated with an increase in immunoreactive VEGF protein, as detected by immunoblot analysis. IGF-I also increased the expression of VEGF mRNA in primary murine osteoblasts, which confirmed that the actions of IGF-I were not unique to SaOS-2 cells. We conclude that IGF-I enhances osteoblast synthesis of VEGF, which may then act locally on endothelium to stimulate angiogenesis, an essential component of bone growth and remodeling.