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生长激素和胰岛素样生长因子I诱导骨形态发生蛋白2和4:在骨骼和牙齿形成中起介导作用?

Growth hormone and insulin-like growth factor I induce bone morphogenetic proteins 2 and 4: a mediator role in bone and tooth formation?

作者信息

Li H, Bartold P M, Zhang C Z, Clarkson R W, Young W G, Waters M J

机构信息

Department of Dentistry, University of Queensland, St. Lucia, Australia.

出版信息

Endocrinology. 1998 Sep;139(9):3855-62. doi: 10.1210/endo.139.9.6211.

DOI:10.1210/endo.139.9.6211
PMID:9724040
Abstract

GH is known to increase the formation of bone and hard tissues of the tooth (dentine, cementum, and enamel), as do bone morphogenetic proteins. GH receptors are expressed in these tissues and could mediate local growth responses. Here we report that both GH and insulin-like growth factor I (IGF-I) are able to increase expression of bone morphogenetic protein-2 and -4 messenger RNAs 4- to 5-fold in human dental pulp fibroblasts in vitro. Induction was seen at physiological concentrations of hormone (25-100 ng/ml GH; 50-200 ng/ml IGF-I) and reached a maximum at 4-8 h. Immunoblot analysis demonstrated that the increase in messenger RNAs resulted in an increase in expressed protein. Anti-IGF-I inhibition experiments indicate that GH is able to induce the response without a requirement for local IGF-I production. These results raise the possibility that bone morphogenetic proteins mediate the local osteogenic actions of GH and IGF-I, and lend support to the view that GH can act through the mediation of factors other than IGF-I. These factors may combine with IGF-I in different tissues to enhance GH action and specificity.

摘要

已知生长激素(GH)能增加骨及牙齿硬组织(牙本质、牙骨质和牙釉质)的形成,骨形态发生蛋白也有此作用。生长激素受体在这些组织中表达,可能介导局部生长反应。在此我们报告,在体外,生长激素和胰岛素样生长因子I(IGF-I)均能使人类牙髓成纤维细胞中骨形态发生蛋白-2和-4信使核糖核酸的表达增加4至5倍。在激素的生理浓度(25 - 100 ng/ml生长激素;50 - 200 ng/ml胰岛素样生长因子I)下即可观察到诱导作用,且在4 - 8小时达到最大值。免疫印迹分析表明,信使核糖核酸的增加导致了表达蛋白的增加。抗胰岛素样生长因子I抑制实验表明,生长激素能够诱导该反应,而无需局部产生胰岛素样生长因子I。这些结果增加了骨形态发生蛋白介导生长激素和胰岛素样生长因子I局部成骨作用的可能性,并支持生长激素可通过胰岛素样生长因子I以外的因子介导发挥作用这一观点。这些因子可能在不同组织中与胰岛素样生长因子I结合,以增强生长激素的作用及特异性。

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