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Title: Androgen receptor (AR) in osteocytes is important for the maintenance of male skeletal integrity: Evidence from targeted AR disruption in mouse osteocytes
Authors: Sinnesael, Mieke ×
Claessens, Frank
Laurent, Michaƫl
Dubois, Vanessa
Boonen, Steven
Deboel, Ludo
Vanderschueren, Dirk #
Issue Date: Dec-2012
Publisher: Blackwell Science, Inc.
Series Title: Journal of Bone and Mineral Research vol:27 issue:12 pages:2535-2543
Abstract: Androgens play a key role in the maintenance of male skeletal integrity. The regulation of this integrity by androgen receptor (AR) signaling has been mainly attributed to osteoblasts. While osteocytes have emerged as key regulators of bone remodeling, the influence of sex steroids on these cells has been poorly studied. We aimed to investigate the role of AR signaling specifically in osteocytes using the Cre/loxP system in male mice (driven by dentin matrix protein 1 (ocy-ARKOs)). Osteocyte fractions of control (AR((ex2)/Y) ) and ocy-ARKO (AR(flox(ex2)/Y) ; DMP1-cre) mice isolated through sequential collagenase digestion showed increasing AR expression towards the mature osteocyte fraction of control males compared to the more immature fractions, whereas this was reduced by >80% in ocy-ARKO osteocytes. The skeletal phenotype of mutant mice was further assessed by histomorphometry and quantitative micro-CT at 12 and 32 weeks of age. Ocy-ARKOs had significantly lower trabecular bone volume and number in femora and tibiae at 32 weeks as well as decreased trabecular number in the L5 vertebra at 12 weeks. Biomechanical testing showed that ocy-ARKO femora were also stiffer and required a lower ultimate force to induce failure at 32 weeks. However, femoral cortical structure was not significantly different at any time point. The absence of AR in osteocyte also did not appear to affect trabecular bone formation neither its response to mechanical loading. In conclusion, selective inactivation of the AR in osteocytes of male mice accelerates age-related deterioration of skeletal integrity. These findings provide evidence for a direct role of androgens in the maintenance of trabecular bone through actions of the AR in osteocytes. © 2012 American Society for Bone and Mineral Research.
URI: 
ISSN: 0884-0431
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Laboratory of Molecular Endocrinology
Clinical and Experimental Endocrinology
× corresponding author
# (joint) last author

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