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Updated: Jun 27, 2026
Osteoclast Derivation from Mouse Bone Marrow
Published on: November 6, 2014
Mineralization and bone resorption are regulated by the androgen receptor in male mice
Cherie Chiang1, Maria Chiu, Alison J Moore
1Department of Medicine, University of Melbourne, Austin Health, Heidelberg, Victoria, Australia.
Abstract:
Androgens play a key role in skeletal growth and bone maintenance; however, their mechanism of action remains unclear. To address this, we selectively deleted the androgen receptor (AR) in terminally differentiated, mineralizing osteoblasts using the Cre/loxP system in mice (osteocalcin-Cre AR knockouts [mOBL-ARKOs]). Male mOBL-ARKOs had decreased femoral trabecular bone volume compared with littermate controls because of a reduction in trabecular number at 6, 12, and 24 wk of age, indicative of increased bone resorption. The effects of AR inactivation in mineralizing osteoblasts was most marked in the young mutant mice at 6 wk of age when rates of bone turnover are high, with a 35% reduction in trabecular bone volume, decreased cortical thickness, and abnormalities in the mineralization of bone matrix, characterized by increased unmineralized bone matrix and a decrease in the amount of mineralizing surface. This impairment in bone architecture in the mOBL-ARKOs persisted throughout adulthood despite an unexpected compensatory increase in osteoblast activity. Our findings show that androgens act through the AR in mineralizing osteoblasts to maintain bone by regulating bone resorption and the coordination of bone matrix synthesis and mineralization, and that this action is most important during times of bone accrual and high rates of bone remodeling.
Insights
Androgen signaling in bone cells is crucial for skeletal growth. Blocking the androgen receptor (AR) in osteoblasts impairs bone formation and increases resorption, highlighting AR
Area of Science:
- Endocrinology
- Bone Biology
- Skeletal Physiology
Background:
- Androgens are vital for bone health and skeletal development.
- The precise mechanism by which androgens influence bone remains incompletely understood.
Purpose of the Study:
- To investigate the role of the androgen receptor (AR) in terminally differentiated, mineralizing osteoblasts.
- To elucidate the specific functions of AR signaling in bone maintenance and remodeling.
Main Methods:
- Utilized a conditional knockout mouse model (osteocalcin-Cre AR knockouts [mOBL-ARKOs]) to selectively delete the AR in osteoblasts.
- Analyzed bone architecture, bone volume, cortical thickness, and mineralization parameters at various ages (6, 12, and 24 weeks).
Main Results:
- Male mOBL-ARKOs exhibited significantly reduced femoral trabecular bone volume, primarily due to decreased trabecular number, indicating heightened bone resorption.
- Bone deficits were most pronounced at 6 weeks, with a 35% reduction in trabecular bone volume, thinner cortices, and impaired matrix mineralization.
- Despite compensatory increases in osteoblast activity, bone architecture abnormalities persisted into adulthood.
Conclusions:
- Androgens act via the AR in mineralizing osteoblasts to maintain bone integrity.
- AR signaling in osteoblasts is critical for regulating bone resorption and coordinating matrix synthesis with mineralization.
- This androgen-osteoblast interaction is particularly important during periods of rapid bone growth and high bone turnover.
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