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BMC Musculoskeletal Disorders
Published in: BMC Musculoskeletal Disorders 1/2007

Open Access 01-12-2007 | Research article

Gene expression analysis in human osteoblasts exposed to dexamethasone identifies altered developmental pathways as putative drivers of osteoporosis

Authors: Conor J Hurson, Joseph S Butler, Dominic T Keating, David W Murray, Denise M Sadlier, John M O'Byrne, Peter P Doran

Published in: BMC Musculoskeletal Disorders | Issue 1/2007

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Abstract

Background

Osteoporosis, a disease of decreased bone mineral density represents a significant and growing burden in the western world. Aging population structure and therapeutic use of glucocorticoids have contributed in no small way to the increase in the incidence of this disease. Despite substantial investigative efforts over the last number of years the exact molecular mechanism underpinning the initiation and progression of osteoporosis remain to be elucidated. This has meant that no significant advances in therapeutic strategies have emerged, with joint replacement surgery being the mainstay of treatment.

Methods

In this study we have used an integrated genomics profiling and computational biology based strategy to identify the key osteoblast genes and gene clusters whose expression is altered in response to dexamethasone exposure. Primary human osteoblasts were exposed to dexamethasone in vitro and microarray based transcriptome profiling completed.

Results

These studies identified approximately 500 osteoblast genes whose expression was altered. Functional characterization of the transcriptome identified developmental networks as being reactivated with 106 development associated genes found to be differentially regulated. Pathway reconstruction revealed coordinate alteration of members of the WNT signaling pathway, including frizzled-2, frizzled-7, DKK1 and WNT5B, whose differential expression in this setting was confirmed by real time PCR.

Conclusion

The WNT pathway is a key regulator of skeletogenesis as well as differentiation of bone cells. Reactivation of this pathway may lead to altered osteoblast activity resulting in decreased bone mineral density, the pathological hallmark of osteoporosis. The data herein lend weight to the hypothesis that alterations in developmental pathways drive the initiation and progression of osteoporosis.
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Metadata
Title
Gene expression analysis in human osteoblasts exposed to dexamethasone identifies altered developmental pathways as putative drivers of osteoporosis
Authors
Conor J Hurson
Joseph S Butler
Dominic T Keating
David W Murray
Denise M Sadlier
John M O'Byrne
Peter P Doran
Publication date
01-12-2007
Publisher
BioMed Central
Published in
BMC Musculoskeletal Disorders / Issue 1/2007
Electronic ISSN: 1471-2474
DOI
https://doi.org/10.1186/1471-2474-8-12

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