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- Title
Inhibition of the Progesterone Nuclear Receptor during the Bone Linear Growth Phase Increases Peak Bone Mass in Female Mice.
- Authors
Yao, Wei; Dai, Weiwei; Shahnazari, Mohammad; Pham, Aaron; Chen, Zhiqiang; Chen, Haiyan; Guan, Min; Lane, Nancy E.
- Abstract
Augmentation of the peak bone mass (PBM) may be one of the most effective interventions to reduce the risk of developing osteoporosis later in life; however treatments to augment PBM are currently limited. Our study evaluated whether a greater PBM could be achieved either in the progesterone nuclear receptor knockout mice (PRKO) or by using a nuclear progesterone receptor (nPR) antagonist, RU486 in mice. Compared to their wild type (WT) littermates the female PRKO mice developed significantly higher cancellous and cortical mass in the distal femurs, and this was associated with increased bone formation. The high bone mass phenotype was partially reproduced by administering RU486 in female WT mice from 1-3 months of age. Our results suggest that the inhibition of the nPR during the rapid bone growth period (1-3 months) increases osteogenesis, which results in acquisition of higher bone mass. Our findings suggest a crucial role for progesterone signaling in bone acquisition and inhibition of the nPR as a novel approach to augment bone mass, which may have the potential to reduce the burden of osteoporosis.
- Subjects
PROGESTERONE receptors; BONE growth; PREVENTION of injuries in older people; DISEASE risk factors; OSTEOPOROSIS; NUCLEAR receptors (Biochemistry); PHENOTYPES; OSTEOCLAST inhibition; BONE fractures; CALCIUM metabolism; LABORATORY mice
- Publication
PLoS ONE, 2010, Vol 5, Issue 7, p1
- ISSN
1932-6203
- Publication type
Article
- DOI
10.1371/journal.pone.0011410