The role of androgens acting via the androgen receptor in osteoblasts to regulate bone cell metabolism
Year: 2017
Type: article
Abstract: Androgens play a key role in skeletal growth and bone maintenance, however their mechanism of action remains unclear.Androgens exert their actions, at least in part, directly via the androgen receptor (AR).This is evidenced by the bone loss observed in male mice with global deletion of the AR (Kawano, Sato et al. 2003).Previous studies have demonstrated that osteoblasts, the bone forming cells, express the AR, however, it is not known at which stage of osteoblast development androgens act.Therefore, the aim of this thesis was to determine the role of androgens acting directly via its molecular target, the AR in 1) proliferating osteoblasts (pOBLs) and 2) terminally differentiated, mineralising osteoblasts (mOBLs) on bone cell metabolism.To achieve this, the DNAbinding dependent actions of the AR were selectively deleted in pOBLs and mOBLs using the Cre/loxP system.Specifically, a) proliferating osteoblast-androgen receptor knockout mice (pOBL-ARKOs) and b) mineralising osteoblast-androgen receptor knockout mice (mOBL-ARKOs) were generated by breeding female AR floxed mice with male mice in which the expression of Cre-recombinase was under the control of the a) osterix or b) osteocalcin promoter respectively.The effect of deletion of the AR from either the proliferating or mineralisation stage of osteoblast development was extensively characterised in skeletally immature, adult and aging pOBL-ARKO and mOBL-ARKO male mice using microCT, static and dynamic histomorphometry and serum biochemical analysis.Initial characterisation of the pOBL-ARKOs determined that deletion of the AR was not Preface Some of the data presented in this thesis was collected in collaboration with others.
Author: Cherie Chiang
Language: English
Topic: Bone Metabolism and Diseases
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W2888325756