Horm Metab Res 2009; 41(11): 822-828
DOI: 10.1055/s-0029-1231056
Original Basic

© Georg Thieme Verlag KG Stuttgart · New York

Combinatory Effects of Androgen Receptor Deficiency and Hind Limb Unloading on Bone

Y. Saita1 , 2 , T. Nakamura3 , F. Mizoguchi1 , 4 , K. Nakashima1 , H. Hemmi1 , T. Hayata1 , Y. Ezura1 , 5 , H. Kurosawa2 , S. Kato3 , M. Noda1 , 4 , 5
  • 1Department of Molecular Pharmacology, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan
  • 2Department of Orthopedics, Juntendo University, School of Medicine, Tokyo, Japan
  • 3Institute of Molecular and Cellular Biosciences, Faculty of Medicine, University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo, Japan
  • 4Global Center of Excellence Program, International Center for Molecular Science in Tooth and Bone Diseases, Tokyo Medical and Dental University, Tokyo, Japan
  • 5Hard Tissue Genome Research Center, Tokyo Medical and Dental University, Tokyo, Japan
Further Information

Publication History

received 13.02.2009

accepted 15.06.2009

Publication Date:
23 July 2009 (eFirst)

Abstract

Male sex hormones play a critical role in regulation of bone metabolism. In male mice lacking androgen receptor (AR), osteopenia and high turnover state in bone remodeling have been reported. However, androgen receptor's role in disuse-induced osteopenia is not known. Therefore, we examined the effects of AR deficiency on unloading-induced bone loss. Wild type or androgen receptor deficient mice (ARKO) were subjected to hind limb unloading (HU) or normal housing (Control). The groups of mice were as follows; wild type control mice (Group WT-Cont), ARKO control mice (Group ARKO-Cont), wild type HU mice (Group WT-HU), and ARKO-HU mice (Group ARKO-HU). HU reduced cancellous bone mass in ARKO (ARKO-HU) by about 70% compared to ARKO-Cont and this reduction rate was over two-fold more than that of wild type (WT-HU) (reduction by less than 30% compared to WT-Cont). Combination of ARKO and HU (ARKO-HU) resulted in the least levels of cortical bone mass and bone mineral density among the four groups. ARKO-HU group indicated the highest levels of systemic bone resorption marker, deoxypyridinoline. Osteoclast development levels in the cultures in ARKO-HU derived bone marrow cells were the highest among the four groups. These data suggest that combination of androgen receptor deficiency and hind limb unloading results in exacerbation of disuse-induced osteopenia due to the enhanced levels of bone resorption.

References

Correspondence

Dr. M. Noda

Department of Molecular Pharmacology

Medical Research Institute

Tokyo Medical and Dental University

3-10 Kanda-Surugadai

2-chome Chiyoda-ku

Tokyo 101

Japan

Phone: +81/3/5280 80 66

Fax: +81/3/5280 80 66

Email: noda.mph@mri.tmd.ac.jp