Androgen receptor action in osteoblasts in male mice is dependent on their stage of maturation

Patricia K. Russell, Michele V. Clarke, Karey Cheong, Paul H. Anderson, Howard A. Morris, Kristine M. Wiren, Jeffrey D. Zajac, Rachel A. Davey

Research output: Contribution to journalArticle

8 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)809-823
Number of pages15
JournalJournal of Bone and Mineral Research
Volume30
Issue number5
DOIs
StatePublished - May 1 2015

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Keywords

  • Bone histomorphometry
  • Genetic animal models
  • Osteoblasts
  • Osteoclasts
  • Sex steroids

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Orthopedics and Sports Medicine

Cite this

Russell, P. K., Clarke, M. V., Cheong, K., Anderson, P. H., Morris, H. A., Wiren, K. M., Zajac, J. D., & Davey, R. A. (2015). Androgen receptor action in osteoblasts in male mice is dependent on their stage of maturation. Journal of Bone and Mineral Research, 30(5), 809-823. https://doi.org/10.1002/jbmr.2413