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中胚层多能细胞系C1中的头蛋白表达及其受骨形态发生蛋白的调控

Noggin expression in a mesodermal pluripotent cell line C1 and its regulation by BMP.

作者信息

Nifuji A, Kellermann O, Noda M

机构信息

Department of Molecular Pharmacology, Medical Research Institute, Tokyo Medical and Dental University, Japan.

出版信息

J Cell Biochem. 1999 Jun 15;73(4):437-44.

Abstract

Osteoblasts and chondrocytes are derived from mesodermal stem cells and their differentiation is under the control of coordinated interaction among signaling molecules. Noggin is one of the signaling molecules which bind to and inactivate BMPs to induce neural tissues and dorsal mesoderm in Xenopus. However, its expression and regulation in mammalian cells has not been known. In this study, we investigated expression of noggin in murine pluripotent mesodermal cell line, C1. Noggin expression was very low in these C1 cells before they were induced to differentiate. When C1 cells were induced to differentiate into chondrocytes in aggregate cultures in the presence of dexamethasone(dex), noggin expression was significantly increased. In a sharp contrast, when the C1 cells were induced to differentiate into osteoblastic cells by the treatment with beta glycerophosphate (betaGP) and ascorbic acid (AA), noggin mRNA expression remained to be barely detectable. Noggin expression was also observed in the developing cartilage of vertebrae in 15.5 dpc mouse embryos. The noggin mRNA level in C1 cells in monolayer cultures was enhanced significantly by the treatment with BMP4/7 in a dose-dependent manner with a maximal effect at 100 ng/ml. The BMP4/7 effect on noggin expression was time dependent starting within 12 h and peaked at 24 h. These results indicate that noggin is expressed in the pluripotent mesodermal cell line C1 and that its expression is regulated by BMP.

摘要

成骨细胞和软骨细胞源自中胚层干细胞,它们的分化受信号分子间协同相互作用的控制。头蛋白是一种信号分子,在非洲爪蟾中,它与骨形态发生蛋白(BMPs)结合并使其失活,从而诱导神经组织和背侧中胚层的形成。然而,其在哺乳动物细胞中的表达和调控尚不清楚。在本研究中,我们调查了头蛋白在小鼠多能中胚层细胞系C1中的表达情况。在这些C1细胞被诱导分化之前,头蛋白的表达非常低。当C1细胞在地塞米松(dex)存在的情况下在聚集培养物中被诱导分化为软骨细胞时,头蛋白的表达显著增加。与之形成鲜明对比的是,当C1细胞通过β-甘油磷酸酯(βGP)和抗坏血酸(AA)处理被诱导分化为成骨细胞时,头蛋白mRNA表达仍几乎检测不到。在15.5天胚胎期的小鼠胚胎发育中的椎骨软骨中也观察到头蛋白的表达。单层培养的C1细胞中的头蛋白mRNA水平通过BMP4/7处理以剂量依赖的方式显著提高,在100 ng/ml时达到最大效应。BMP4/7对头蛋白表达的影响具有时间依赖性,在12小时内开始,24小时达到峰值。这些结果表明头蛋白在多能中胚层细胞系C1中表达,并且其表达受BMP调控。

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