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Global transcriptome analysis in mouse calvarial osteoblasts highlights sets of genes regulated by modeled microgravity and identifies a “mechanoresponsive osteoblast gene signature”

Global transcriptome analysis in mouse calvarial osteoblasts highlights sets of genes regulated... Mechanical unloading is known to be detrimental for the skeleton, but the underlying molecular mechanisms are not fully elucidated. We performed global transcriptome analysis of mouse calvarial osteoblasts grown for 5 days at unit gravity (1g) or under modeled microgravity (0.008g) in the NASA‐developed rotating wall vessel (RWV) bioreactor. Elaboration of gene profiling data evidenced that, among the >20,000 gene probes evaluated, 45 genes were significantly up‐regulated (cut‐off >2) and 88 were down‐regulated (cut‐off <0.5) in modeled microgravity versus 1g. This set of regulated genes includes genes involved in osteoblast differentiation, function, and osteoblast–osteoclast cross‐talk, as well as new genes not previously correlated with bone metabolism. Microarray data were validated for subsets of genes by real‐time RT‐PCR, Western blot, or functional analysis. The significantly modulated genes were then clustered using the GOTM (Gene Ontology Tree Machine) software. This analysis evidenced up‐regulation of genes involved in the induction of apoptosis, in response to stress and in the activity of selected growth factors. Other molecular functions, such as extracellular matrix structural constituent, glycosaminoglycan/heparin‐binding activity, and other growth factor activity, were instead down‐regulated. We finally matched our transcriptome results with other public global gene profiles obtained in loading and unloading conditions, identifying 10 shared regulated genes which could represent an “osteoblast mechanoresponsive gene signature.” J. Cell. Biochem. 107: 240–252, 2009. © 2009 Wiley‐Liss, Inc. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Journal of Cellular Biochemistry Wiley

Global transcriptome analysis in mouse calvarial osteoblasts highlights sets of genes regulated by modeled microgravity and identifies a “mechanoresponsive osteoblast gene signature”

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References (61)

Publisher
Wiley
Copyright
Copyright © 2009 Wiley Subscription Services, Inc., A Wiley Company
ISSN
0730-2312
eISSN
1097-4644
DOI
10.1002/jcb.22120
pmid
19288527
Publisher site
See Article on Publisher Site

Abstract

Mechanical unloading is known to be detrimental for the skeleton, but the underlying molecular mechanisms are not fully elucidated. We performed global transcriptome analysis of mouse calvarial osteoblasts grown for 5 days at unit gravity (1g) or under modeled microgravity (0.008g) in the NASA‐developed rotating wall vessel (RWV) bioreactor. Elaboration of gene profiling data evidenced that, among the >20,000 gene probes evaluated, 45 genes were significantly up‐regulated (cut‐off >2) and 88 were down‐regulated (cut‐off <0.5) in modeled microgravity versus 1g. This set of regulated genes includes genes involved in osteoblast differentiation, function, and osteoblast–osteoclast cross‐talk, as well as new genes not previously correlated with bone metabolism. Microarray data were validated for subsets of genes by real‐time RT‐PCR, Western blot, or functional analysis. The significantly modulated genes were then clustered using the GOTM (Gene Ontology Tree Machine) software. This analysis evidenced up‐regulation of genes involved in the induction of apoptosis, in response to stress and in the activity of selected growth factors. Other molecular functions, such as extracellular matrix structural constituent, glycosaminoglycan/heparin‐binding activity, and other growth factor activity, were instead down‐regulated. We finally matched our transcriptome results with other public global gene profiles obtained in loading and unloading conditions, identifying 10 shared regulated genes which could represent an “osteoblast mechanoresponsive gene signature.” J. Cell. Biochem. 107: 240–252, 2009. © 2009 Wiley‐Liss, Inc.

Journal

Journal of Cellular BiochemistryWiley

Published: Mar 15, 2010

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