Zhong Zhendong A, Kot Alexander, Lay Yu-An E, Zhang Hongliang, Jia Junjing, Lane Nancy E, Yao Wei
Center for Musculoskeletal Health, Department of Internal Medicine, University of California Davis Medical Center, Sacramento, CA, USA.
Center for Cancer and Cell Biology, Program in Skeletal Disease and Tumor Microenvironment, Van Andel Research Institute, Grand Rapids, MI, USA.
J Bone Miner Res. 2017 Sep;32(9):1841-1852. doi: 10.1002/jbmr.3186. Epub 2017 Jul 13.
The role of the progesterone receptor (PR) in the regulation of sexual dimorphism in bone has yet to be determined. Here we utilized genetic fate mapping and Western blotting to demonstrate age-dependent PR expression in the mouse femoral metaphysis and diaphysis. To define sex-dependent and osteoblast stage-specific effects of PR on bone acquisition, we selectively deleted PR at different stages of osteoblast differentiation. We found that when Prx1-Cre mice were crossed with PR floxed mice to generate a mesenchymal stem cell (MSC) conditional KO model (Prx1; PRcKO), the mutant mice developed greater trabecular bone volume with higher mineral apposition rate and bone formation. This may be explained by increased number of MSCs and greater osteogenic potential, particularly in males. Age-related trabecular bone loss was similar between the Prx1; PRcKO mice and their WT littermates in both sexes. Hormone deficiency during the period of rapid bone growth induced rapid trabecular bone loss in both the WT and the Prx1; PRcKO mice in both sexes. No differences in trabecular bone mass was observed when PR was deleted in mature osteoblasts using osteocalcin-Cre (Bglap-Cre). Also, there were no differences in cortical bone mass in all three PRcKO mice. In conclusion, PR inactivation in early osteoprogenitor cells but not in mature osteoblasts influenced trabecular bone accrual in a sex-dependent manner. PR deletion in osteoblast lineage cells did not affect cortical bone mass. © 2017 American Society for Bone and Mineral Research.
孕激素受体（PR）在骨骼性二态性调节中的作用尚未确定。在此，我们利用遗传命运图谱和蛋白质免疫印迹法来证明PR在小鼠股骨干骺端和骨干中表达具有年龄依赖性。为了确定PR对骨量获取的性别依赖性和成骨细胞阶段特异性影响，我们在成骨细胞分化的不同阶段选择性地敲除PR。我们发现，当Prx1-Cre小鼠与PR基因敲除小鼠杂交以生成间充质干细胞（MSC）条件性敲除模型（Prx1；PRcKO）时，突变小鼠的小梁骨体积更大，矿化沉积率和骨形成更高。这可能是由于MSC数量增加和成骨潜力更大，尤其是在雄性小鼠中。Prx1；PRcKO小鼠与其野生型同窝小鼠在两性中的年龄相关性小梁骨丢失相似。在快速骨生长期间的激素缺乏在两性的野生型和Prx1；PRcKO小鼠中均诱导了快速小梁骨丢失。当使用骨钙素-Cre（Bglap-Cre）在成熟成骨细胞中敲除PR时，未观察到小梁骨量的差异。此外，在所有三种PRcKO小鼠中皮质骨量也没有差异。总之，早期骨祖细胞而非成熟成骨细胞中的PR失活以性别依赖性方式影响小梁骨的积累。成骨细胞谱系细胞中的PR缺失不影响皮质骨量。©2017美国骨与矿物质研究学会。
