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Physiol. Genomics 33: 301-311, 2008. First published March 11, 2008; doi:10.1152/physiolgenomics.00028.2008
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Received 30 January 2008; accepted in final form 6 March 2008.
Physiological Genomics 33:301-311 (2008)
1094-8341/08 $8.00 © 2008 American Physiological Society

Systematic assessment of the human osteoblast transcriptome in resting and induced primary cells

Elin Grundberg1,2, Helena Brändström3, Kevin C. L. Lam1, Scott Gurd1, Bing Ge1, Eef Harmsen1, Andreas Kindmark3, Östen Ljunggren3, Hans Mallmin4, Olle Nilsson4 and Tomi Pastinen1,2

1 McGill University and Genome Quebec Innovation Centre, Montreal, Canada
2 Department of Human Genetics, McGill University, Montreal, Canada
3 Department of Medical Sciences Uppsala University, Uppsala, Sweden
4 Department of Surgical Sciences, Uppsala University, Uppsala, Sweden

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.

gene expression; fibroblasts; bone morphogenic protein-2; dexamethasone







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