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JOURNAL

Gene Regulation and Systems Biology

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Regulatory Mechanisms in Bone Following Mechanical Loading

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Publication Date: 17 Jan 2012

Type: Original Research

Journal: Gene Regulation and Systems Biology

Citation: Gene Regulation and Systems Biology 2012:6 43-53

doi: 10.4137/GRSB.S8068

Abstract

Bone responds with increased bone formation to mechanical loading, and the time course of bone formation after initiating mechanical loading is well characterized. However, the regulatory activities governing the loading-dependent changes in gene expression are not well understood. The goal of this study was to identify the time-dependent regulatory mechanisms that governed mechanical loading-induced gene expression in bone using a predictive bioinformatics algorithm. A standard model for bone loading in rodents was employed in which the right forelimb was loaded axially for three minutes per day, while the left forearm served as a non-loaded, contralateral control. Animals were subjected to loading sessions every day, with 24 hours between sessions. Ulnas were sampled at 11 time points, from 4 hours to 32 days after beginning loading. Using a predictive bioinformatics algorithm, we created a linear model of gene expression and identified 44 transcription factor binding motifs and 29 microRNA binding sites that were predicted to regulate gene expression across the time course. Known and novel transcription factor binding motifs were identified throughout the time course, as were several novel microRNA binding sites. These time-dependent regulatory mechanisms may be important in controlling the loading-induced bone formation process.



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The reviewing and editorial management of our paper was timely, thorough, and systematic.  In particular the reviewers' comments resulted in a paper significantly more robust than the first version.
Dr Clark D Jeffries (University of North Carolina at Chapel Hill, Chapel Hill, NC, USA)
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