title: The reduced trabecular bone mass of adult ARKO male mice results from the decreased osteogenic differentiation of bone marrow stroma cells.
abstract: Male mice with androgen receptor knock-out (ARKO) show significant bone loss at a young age. However, the lasting effect of AR inactivation on bone in aging male mice remains unclear. We designed this study to evaluate the effect of AR on bone quality in aging male mice and to find the possible causes of AR inactivation contributing to the bone loss. The mice were grouped according to their ages and AR status and their trabecular bones were examined by micro-CT analysis at 6, 12, 18, and 30 weeks old. We found that bone mass consistently decreased and the bone microarchitectures continuously deteriorated in male ARKO mice at designated time points. To determine the cause of the bone loss in ARKO mice, we further examined the role of AR in bone cell fate decision and differentiation and we conducted experiments on bone marrow stromal cells (BMSC) obtained from wild type (WT) and AR knockout (KO) mice. We found that ARKO mice had higher numbers of colony formation unit-fibroblast (CFU-F), and CD44 and CD34 positive cells in bone marrow than WT mice. Our Q-RT-PCR results showed lower expression of genes linked to osteogenesis in BMSCs isolated from ARKO mice. In conclusion, AR nullification disrupted bone microarchitecture and caused trabecular bone mass loss in male ARKO mice. And the fate of BMSCs was impacted by the loss of AR. Therefore, these findings suggest that AR may accelerate the use of progenitor cells and direct them into osteogenic differentiation to affect bone metabolism.
authors: Center for Menopause and Reproductive Medicine Research, Department of Obstetrics and Gynecology, Kaohsiung Chang-Gung Memorial Hospital, Kaohsiung, Taiwan.
authors: Meng-Yin
authors: MY
authors: Tsai
authors: Chih-Rong
authors: CR
authors: Shyr
authors: Hong-Yo
authors: HY
authors: Kang
authors: Yung-Chiao
authors: YC
authors: Chang
authors: Pei-Lin
authors: PL
authors: Weng
authors: Shu-Yo
authors: SY
authors: Wang
authors: Ko-En
authors: KE
authors: Huang
authors: Chawnshang
authors: C
authors: Chang
mesh_terms: D000375:Aging / Q000235:genetics / Q000473:pathology; D000818:Animals; D001854:Bone Marrow Cells / Q000473:pathology; D001842:Bone and Bones / Q000000981:diagnostic imaging / Q000473:pathology*; D002454:Cell Differentiation / Q000235:genetics; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009929:Organ Size; D010006:Osteoblasts / Q000473:pathology; D010012:Osteogenesis / Q000235:genetics*; D010024:Osteoporosis / Q000000981:diagnostic imaging / Q000235:genetics* / Q000473:pathology; D011859:Radiography; D011944:Receptors, Androgen / Q000235:genetics*; D013234:Stem Cells / Q000473:pathology; D017154:Stromal Cells / Q000473:pathology
chemical_list: D011944:Receptors, Androgen