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Chunk #37 — DISCUSSION

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Identification of novel bone-specific molecular targets of binge alcohol and ibandronate by transcriptome analysis.
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Quality Threshold (QT) clustering, which allowed the visualization of all existing patterns of gene expression occurring in the acute binge alcohol differentially expressed gene list was used for signature identification. A gene cluster which provided insight into the protective effects of antiresorptive treatment on alcohol-related bone loss was identified from the alcohol plus ibandronate (AI) treatment group. This cluster is comprised of genes showing both significant differential expression in the chronic binge alcohol group and a significant normalization of expression levels (to control levels) in the AI group. This gene expression profile parallels the pattern of bone loss and prevention of loss in the AI group shown by BMD and compressive strength analysis. The observation that ibandronate mediates both the prevention of alcohol-related bone loss and the normalization of a subset of alcohol-perturbed gene expression profiles in bone is unique and has not been previously reported. This observation is supported by a previous unrelated study which showed normalization of disease-related changes in gene expression related to therapeutic intervention in an examination of cytokine transcript levels associated with mucosal inflammatory tissue