Human Gene Set: KANG_AR_TARGETS_DN

For the Mouse gene set with the same name, see KANG_AR_TARGETS_DN

Standard name KANG_AR_TARGETS_DN
Systematic name M2225
Brief description Genes down-regulated in osteoblasts from wild type male mice compared to those with AR [GeneID=367] knockout.
Full description or abstract While androgen receptor (AR)-deficient mice developed osteopenia in endochondral bones due to the high bone turnover with increased bone resorption by osteoclasts, little is known about the mechanism of intramembranous bone loss contributed by AR in osteoblasts. Here, we discovered a dramatic decrease in the area of calcification, new bone, and the number of osteocytes in calvaria from AR-deficient mice related to a reduction in mineralization caused, in part, by the diminished activity of AR-deficient osteoblasts. Enforced AR expression in differentiated osteoblasts boosts mineralization while knockdown of AR expression prevents androgen-induced mineralization. We identified the tissue-nonspecific alkaline phosphatase (TNSALP) and several members of small integrin binding ligand N-linked glycoprotein (SIBLING) gene family as androgen target genes required for AR-mediated bone formation. We show that inorganic phosphate (P(i)) levels and TNSALP activity increased in response to androgen/AR and P(i) signals increase the expression and translocation of AR. The ectopic expression of TNSALP or P(i) partially rescued the bone loss due to AR deficiency. Thus, androgen/AR signaling plays an essential role in bone formation by coordinating the expression of genes associated with phosphate regulation.
Collection C2: Curated
      CGP: Chemical and Genetic Perturbations
Source publication Pubmed 18838539   Authors: Kang HY,Shyr CR,Huang CK,Tsai MY,Orimo H,Lin PC,Chang C,Huang KE
Exact source Table 2S: Fold < 1
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Source species Mus musculus
Contributed by Arthur Liberzon (MSigDB Team)
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Version history 3.1: First introduced

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