Sex dimorphic regulation of osteoprogenitor progesterone in bone stromal cells

被引：12

作者：

Kot, Alexander ^{[1
]}

Zhong, Zhendong A. ^{[1
,2
]}

Zhang, Hongliang ^{[1
,3
]}

Lay, Yu-An Evan ^{[1
]}

Lane, Nancy E. ^{[1
]}

Yao, Wei ^{[1
]}

机构：

[1] Univ Calif Davis, Med Ctr, Dept Internal Med, Ctr Musculoskeletal Hlth, Sacramento, CA 95817 USA

[2] Van Andel Res Inst, Ctr Canc & Cell Biol, Program Skeletal Dis & Tumor Microenvironm, Grand Rapids, MI USA

[3] Cent S Univ, Xiangya Hosp 2, Ctr Difficult Diagnoses & Rare Dis, Dept Emergency Med, Changsha, Hunan, Peoples R China

来源：

JOURNAL OF MOLECULAR ENDOCRINOLOGY | 2017年 / 59卷 / 04期

关键词：

progesterone receptor; osteoprogenitor; signaling pathways; RNA-seq; bone; DEPOT MEDROXYPROGESTERONE ACETATE; PROTEIN-KINASE-A; CALCIUM SUPPLEMENTATION; MINERAL DENSITY; OSTEOBLAST DIFFERENTIATION; EXPRESSION ANALYSIS; PHYSICAL-ACTIVITY; CONTROLLED-TRIAL; XENOPUS OOCYTES; GROWTH-FACTOR;

D O I：

10.1530/JME-17-0076

中图分类号：

R5 [内科学];

学科分类号：

100201 [内科学];

摘要：

Increasing peak bone mass is a promising strategy to prevent osteoporosis. A mouse model of global progesterone receptor (PR) ablation showed increased bone mass through a sex-dependent mechanism. Cre-Lox recombination was used to generate a mouse model of osteoprogenitor-specific PR inactivation, which recapitulated the high bone mass phenotype seen in the PR global knockout mouse mode. In this work, we employed RNA sequencing analysis to evaluate sex-independent and sex-dependent differences in gene transcription of osteoprogenitors of wild-type and PR conditional knockout mice. PR deletion caused marked sex hormone-dependent changes in gene transcription in male mice as compared to wild-type controls. These transcriptional differences revealed dysregulation in pathways involving immunomodulation, osteoclasts, bone anabolism, extracellular matrix interaction and matrix interaction. These results identified many potential mechanisms that may explain our observed high bone mass phenotype with sex differences when PR was selectively deleted in the MSCs.

引用

页码：351 / 363

页数：13

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