title: Inactivation of the androgen receptor in bone-forming cells leads to trabecular bone loss in adult female mice.
abstract: Removal of the androgen receptor (AR) from bone-forming cells has been shown to reduce trabecular bone volume in male mice. In female mice, the role of AR in the regulation of bone homeostasis has been poorly understood. We generated a mouse strain in which the AR is completely inactivated only in mineralizing osteoblasts and osteocytes by breeding mice carrying osteocalcin promoter-regulated Cre-recombinase with mice possessing loxP recombination sites flanking exon 2 of the AR gene (AR(ΔOB/ΔOB) mice). In female AR(ΔOB/ΔOB) mice, the trabecular bone volume was reduced owing to a smaller number of trabeculae at 6 months of age compared with the control AR(fl/fl) animals. In male AR(ΔOB/ΔOB) mice, an increase in trabecular bone separation could already be detected at 3.5 months of age, and at 6 months, the trabecular bone volume was significantly reduced compared with that of male AR(fl/fl) mice. No AR-dependent changes were observed in the cortical bone of either sex. On the basis of micro-computed tomography and histomorphometry, we conclude that in male mice, the AR is involved in the regulation of osteoclast number by osteoblasts, whereas in female mice, the lack of the AR in the bone-forming cells leads to a decreased number of trabeculae upon aging.
authors.affiliation: Department of Cell Biology and Anatomy, Institute of Biomedicine, University of Turku , Turku, Finland ; Turku Center for Disease Modeling, University of Turku , Turku, Finland.
authors.forename: Jorma A
authors.initials: JA
authors.lastname: Määttä
authors.affiliation: Department of Cell Biology and Anatomy, Institute of Biomedicine, University of Turku , Turku, Finland.
authors.forename: Kalman G
authors.initials: KG
authors.lastname: Büki
authors.affiliation: Department of Cell Biology and Anatomy, Institute of Biomedicine, University of Turku , Turku, Finland.
authors.forename: Kaisa K
authors.initials: KK
authors.lastname: Ivaska
authors.affiliation: Department of Cell Biology and Anatomy, Institute of Biomedicine, University of Turku , Turku, Finland.
authors.forename: Vappu
authors.initials: V
authors.lastname: Nieminen-Pihala
authors.affiliation: Department of Cell Biology and Anatomy, Institute of Biomedicine, University of Turku , Turku, Finland.
authors.forename: Teresa D
authors.initials: TD
authors.lastname: Elo
authors.affiliation: Department of Cell Biology and Anatomy, Institute of Biomedicine, University of Turku , Turku, Finland.
authors.forename: Tiina
authors.initials: T
authors.lastname: Kähkönen
authors.affiliation: Turku Center for Disease Modeling, University of Turku , Turku, Finland ; Department of Physiology, Institute of Biomedicine, University of Turku , Turku, Finland.
authors.forename: Matti
authors.initials: M
authors.lastname: Poutanen
authors.affiliation: Department of Cell Biology and Anatomy, Institute of Biomedicine, University of Turku , Turku, Finland.
authors.forename: Pirkko
authors.initials: P
authors.lastname: Härkönen
authors.affiliation: Department of Cell Biology and Anatomy, Institute of Biomedicine, University of Turku , Turku, Finland.
authors.forename: Kalervo
authors.initials: K
authors.lastname: Väänänen