Systematic assessment of the human osteoblast transcriptome in resting and induced primary cells
Systematic assessment of the human osteoblast transcriptome in resting and induced primary cells
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DOI：
10.1152/physiolgenomics.00028.2008
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发表时间：
2008-05-13
影响因子：
4.6
通讯作者：
Pastinen, Tomi
中科院分区：
文献类型：
--
作者：
Grundberg, Elin;Brandstrom, Helena;Pastinen, Tomi
成骨细胞是骨重建的关键参与者。人原代成骨细胞样细胞（HObs）从骨外植体的可及性使他们成为一个有利可图的模型，用于研究骨转换的分子生理学，发现新的合成代谢疗法，以及间充质细胞生物学。关于HObs的静息和动态表达谱知之甚少，迄今为止还没有进行系统评估成骨细胞转录组的研究。本研究的目的是表征HOBs和研究信号级联和基因网络与静息和骨形态发生蛋白（BMP）-2-和地塞米松诱导的细胞的全基因组表达谱。此外，我们将HOb基因表达与基因表达综合库中公开的样本进行了比较。我们的数据显示，与密切相关的细胞（如成纤维细胞或软骨细胞）相比，大量的基因和网络主要在HOb中表达。例如，胰岛素样生长因子（IGF）信号通路中的基因在HOb中富集（P = 0.003），包括结合蛋白（IGFBP-1，-2，-5）和IGF-II及其受体。另一种HOb特异性表达模式包括瘦素及其受体（P < 10（-8））。此外，在用BMP-2或地塞米松刺激HOb后，观察到几个感兴趣的基因和途径的表达。例如，我们的数据支持外周瘦素信号传导在骨细胞功能中的作用。总之，我们提供了景观的组织特异性和动态基因表达的HOBS。这一资源将允许利用成骨细胞作为模型来研究与人类骨生理学和疾病相关的特定基因网络和基因家族。
Osteoblasts are key players in bone remodeling. The accessibility of human primary osteoblast-like cells (HObs) from bone explants makes them a lucrative model for studying molecular physiology of bone turnover, for discovering novel anabolic therapeutics, and for mesenchymal cell biology in general. Relatively little is known about resting and dynamic expression profiles of HObs, and to date no studies have been conducted to systematically assess the osteoblast transcriptome. The aim of this study was to characterize HObs and investigate signaling cascades and gene networks with genomewide expression profiling in resting and bone morphogenic protein (BMP)-2-and dexamethasone-induced cells. In addition, we compared HOb gene expression with publicly available samples from the Gene Expression Omnibus. Our data show a vast number of genes and networks expressed predominantly in HObs compared with closely related cells such as fibroblasts or chondrocytes. For instance, genes in the insulin-like growth factor (IGF) signaling pathway were enriched in HObs (P = 0.003) and included the binding proteins (IGFBP-1, -2, -5) and IGF-II and its receptor. Another HOb-specific expression pattern included leptin and its receptor (P < 10(-8)). Furthermore, after stimulation of HObs with BMP-2 or dexamethasone, the expression of several interesting genes and pathways was observed. For instance, our data support the role of peripheral leptin signaling in bone cell function. In conclusion, we provide the landscape of tissue-specific and dynamic gene expression in HObs. This resource will allow utilization of osteoblasts as a model to study specific gene networks and gene families related to human bone physiology and diseases.