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Title: Identification of gene pathways altered by deletion of the androgen receptor specifically in mineralizing osteoblasts and osteocytes in mice.
Austin Authors: Russell, Patricia K;Clarke, Michele V;Skinner, Jarrod P;Pang, Tammy P S;Zajac, Jeffrey D ;Davey, Rachel A
Affiliation: Department of Medicine, Austin Health, University of Melbourne, Studley Road, Heidelberg, Victoria 3084, Australia
Issue Date: 29-May-2012
Publication information: Journal of Molecular Endocrinology 2012; 49(1): 1-10
Abstract: Androgens play a key role in skeletal growth and maintenance in males and can mediate their actions, at least in part, via the androgen receptor (AR) in osteoblasts. To investigate the mechanisms by which androgens exert their effects via the AR in mineralizing osteoblasts and osteocytes, we identified gene targets/pathways regulated by the AR using targeted gene expression and microarray approaches on bone isolated from mice in which the AR is specifically deleted in mineralizing osteoblasts and osteocytes (mOBL-ARKOs). Gene ontology mining indicated a number of biological processes to be affected in the bones of mOBL-ARKOs including skeletal and muscular system development and carbohydrate metabolism. All genes identified to have altered expression in the bones of mOBL-ARKOs were confirmed by Q-PCR for their androgen responsiveness in an androgen deprivation and replacement mouse model. The osteoblast genes Col1a1 and Bglap and the osteoclast genes Ctsk and RANKL (Tnfs11) were upregulated in the bones of mOBL-ARKOs, consistent with the increased matrix synthesis, mineralization, and bone resorption observed previously in these mice. Of significant interest, we identified genes involved in carbohydrate metabolism (adiponectin and Dpp4) and in growth and development (GH, Tgfb (Tgfb2), Wnt4) as potential targets of androgen action via the AR in mineralizing osteoblasts.
Gov't Doc #: 22525354
DOI: 10.1530/JME-12-0014
Journal: Journal of molecular endocrinology
Type: Journal Article
Subjects: Adiponectin.blood
Blood Glucose
Calcification, Physiologic
Gene Deletion
Gene Expression Profiling
Gene Targeting
Mice, Inbred C57BL
Mice, Knockout
Microarray Analysis
Receptors, Androgen.genetics.metabolism
Signal Transduction
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