Inhibition of the progesterone nuclear receptor during the bone linear growth phase increases peak bone mass in female mice

Wei Yao, Weiwei Dai, Mohammad Shahnazari, Aaron Pham, Zhiqiang Chen, Haiyan Chen, Min Guan, Nancy E Lane

Research output: Contribution to journalArticle

24 Citations (Scopus)

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.

Original languageEnglish (US)
Article numbere11410
JournalPLoS One
Volume5
Issue number7
DOIs
StatePublished - 2010

Fingerprint

Bone Development
Progesterone Receptors
Cytoplasmic and Nuclear Receptors
Progesterone
progesterone
Bone
bones
Bone and Bones
receptors
mice
Osteogenesis
osteoporosis
Knockout Mice
Osteoporosis
bone formation
Femur
femur
antagonists
phenotype

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Inhibition of the progesterone nuclear receptor during the bone linear growth phase increases peak bone mass in female mice. / Yao, Wei; Dai, Weiwei; Shahnazari, Mohammad; Pham, Aaron; Chen, Zhiqiang; Chen, Haiyan; Guan, Min; Lane, Nancy E.

In: PLoS One, Vol. 5, No. 7, e11410, 2010.

Research output: Contribution to journalArticle

Yao, Wei ; Dai, Weiwei ; Shahnazari, Mohammad ; Pham, Aaron ; Chen, Zhiqiang ; Chen, Haiyan ; Guan, Min ; Lane, Nancy E. / Inhibition of the progesterone nuclear receptor during the bone linear growth phase increases peak bone mass in female mice. In: PLoS One. 2010 ; Vol. 5, No. 7.
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AU - Chen, Haiyan

AU - Guan, Min

AU - Lane, Nancy E

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