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

PloS One
Wei YaoNancy E Lane

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.

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Citations

Aug 12, 2014·Calcified Tissue International·Tzu-Cheng LeeYoungho Seo
May 26, 2012·The Journal of Physiological Sciences : JPS·Kannikar WongdeeNarattaphol Charoenphandhu
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Mar 31, 2015·Clinical Orthopaedics and Related Research·Weiwei DaiWei Yao
Jun 2, 2017·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Zhendong A ZhongWei Yao
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Apr 27, 2020·Molecular Biology Reports·Maryam SoltanyzadehMarzieh Ghollasi
Apr 27, 2021·Endocrine Reviews·Edouard G MillsAlexander N Comninos

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Methods Mentioned

BETA
PCR
genotyping
X-ray
enzyme-linked immunosorbent assay

Software Mentioned

SCION IMAGE
GraphPad Prism
Bioquant Image Analysis
SPSS

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