Gene Expression Analysis in Human Osteoblasts Exposed to Dexamethasone Identifies Altered Developmental Pathways as Putative Drivers of Osteoporosis
BMC Musculoskeletal Disorders Vol 8
An Open Access research article from BMC
Published 12 February 2007
Abstract (provisional)
BackgroundOsteoporosis, 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 skeltonogenesis 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.
The complete article is available as a provisional PDF. The fully formatted PDF and HTML versions are in production.
BMC Musculoskeletal Disorders 2007, 8:12 doi:10.1186/1471-2474-8-12
Mosie Baby Kit receives class 2 FDA clearance for intravaginal insemination
December 6th 2023Discover how Mosie Baby's at-home insemination kit, the first FDA-cleared of its kind, empowers individuals facing infertility challenges with an effective, easy-to-use solution for intravaginal insemination.
Read More
Daré Bioscience initiates phase 3 clinical trial for ovaprene contraceptive
December 5th 2023Daré Bioscience has commenced a pivotal phase 3 clinical trial for ovaprene, an intravaginal contraceptive that releases a locally acting agent to prevent sperm entry into the cervical canal, marking a significant step towards a non-hormonal contraceptive option for women.
Read More
Exploring menstrual health: Insights from the Avon longitudinal study
December 5th 2023Unveiling a comprehensive analysis of menstrual cycle characteristics in mothers and daughters, this article delves into the diverse features, potential risk factors, and the importance of understanding these nuances for effective menstrual health management.
Read More
How plasma biomarkers illuminate brain health in women with HIV
December 4th 2023Discoveries from a comprehensive study reveal specific plasma biomarkers that may serve as indicators of neurological well-being in individuals living with HIV, shedding light on potential links to Alzheimer's disease and emphasizing the importance of early detection for improved outcomes.
Read More