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Title: Androgen receptor action in osteoblasts in male mice is dependent on their stage of maturation.
Austin Authors: Russell, Patricia K;Clarke, Michele V;Cheong, Karey;Anderson, Paul H;Morris, Howard A;Wiren, Kristine M;Zajac, Jeffrey D ;Davey, Rachel A
Affiliation: Department of Medicine, Austin Health, University of Melbourne, Heidelberg, Australia
Issue Date: 1-May-2015
Publication information: Journal of Bone and Mineral Research : the Official Journal of the American Society For Bone and Mineral Research; 30(5): 809-23
Abstract: Androgen action via the androgen receptor (AR) is essential for normal skeletal growth and bone maintenance post-puberty in males; however, the molecular and cellular mechanisms by which androgens exert their actions in osteoblasts remains relatively unexplored in vivo. To identify autonomous AR actions in osteoblasts independent of AR signaling in other tissues, we compared the extent to which the bone phenotype of the Global-ARKO mouse was restored by replacing the AR in osteoblasts commencing at either the 1) proliferative or 2) mineralization stage of their maturation. In trabecular bone, androgens stimulated trabecular bone accrual during growth via the AR in proliferating osteoblasts and maintained trabecular bone post-puberty via the AR in mineralizing osteoblasts, with its predominant action being to inhibit bone resorption by decreasing the ratio of receptor activator of NF-κB ligand (RANKL) to osteoprotegerin (OPG) gene expression. During growth, replacement of the AR in proliferating but not mineralizing osteoblasts of Global-ARKOs was able to partially restore periosteal circumference, supporting the concept that androgen action in cortical bone to increase bone size during growth is mediated via the AR in proliferating osteoblasts. This study provides further significant insight into the mechanism of androgen action via the AR in osteoblasts, demonstrating that it is dependent on the stage of osteoblast maturation. © 2014 American Society for Bone and Mineral Research.
Gov't Doc #: 25407961
DOI: 10.1002/jbmr.2413
Type: Journal Article
Appears in Collections:Journal articles

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