Interaction of epidermal growth factor and insulin-like growth factor-1 in the regulation of growth plate chondrocytes

Interaction of epidermal growth factor and insulin-like growth factor-1 in the regulation of growth plate chondrocytes
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DOI:
10.1006/excr.1997.3574
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发表时间:
1997-07-10
影响因子:
3.7
通讯作者:
Trippel, SB
Trippel, SB
中科院分区:
医学3区
文献类型:
--
作者:
Bonassar, LJ;Trippel, SB

文献摘要

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生长因子对骨痂生长板细胞的作用是调节骨骼生长的重要机制。胰岛素样生长因子-I(IGF-I)在骨生长调节中发挥重要作用。相比之下,表皮生长因子(EGF)的作用(如果有的话)还不清楚。在这些研究中,我们验证了EGF与IGF-I在生长板软骨细胞有丝分裂和代谢活动调节中相互作用的假设。从牛放射尺骨生长板分离的软骨细胞在悬浮培养中培养,分析了它们对EGF的反应性,包括DNA、蛋白质和蛋白多糖的合成,对IGF-I的反应性,以及特异性结合[I-125]-IGF-I的能力。用最大有效浓度(10-100 ng/ml)的EGF处理生长板软骨细胞,可使[I-125]IGF-I的特异性结合增加16-27%。Scatchard分析表明,这种特异性结合的增加是由于受体/细胞数量的增加,而受体亲和力没有变化。EGF对蛋白质合成的促进作用为30-35%。EGF可增加软骨细胞对IGF-I的反应性,使IGF-I刺激的有丝分裂活性和蛋白多糖合成分别增加90%和60%。鉴于IGF-I在骨骼发育中的重要作用,以及生长板中EGF的存在,本研究提示这些生长因子之间的相互作用在骨骼生长调节中具有重要作用。(C)1997年学术出版社。
The action of growth factors on the cells of the epiphyseal growth plate is an important mechanism in the regulation of skeletal growth. Insulin-like growth factor-I (IGF-I) is known to play a central role in the regulation of bone growth. In contrast, the role, if any, of epidermal growth factor (EGF) is not yet clear. In these studies, we tested the hypothesis that EGF interacts with IGF-I in the regulation of growth plate chondrocyte mitotic and metabolic activities. Chondrocytes isolated from bovine radioulnar growth plates and incubated in suspension culture were analyzed for their responsiveness to EGF with respect to synthesis of DNA, proteins, and proteoglycans, responsiveness to IGF-I, and ability to specifically bind [I-125]-IGF-I. Treatment of growth plate chondrocytes with maximally effective concentrations (10-100 ng/ml) of EGF produced a 16-27% increase in specific binding of [I-125]IGF-I. Scatchard analysis indicated that this increase in specific binding was due to an increase in the number of receptors/cell with no change in receptor affinity. EGF stimulated protein synthesis by 30-35%. Pretreatment with EGF increased the responsiveness of chondrocytes to IGF-I, resulting in 90 and 60% augmentation of IGF-I-stimulated mitotic activity and proteoglycan synthesis, respectively. Given the prominent role of IGF-I in skeletal development and the presence of EGF in the growth plate, this study suggests an important role for interactions between these growth factors in the regulation of skeletal growth. (C) 1997 Academic Press.