Rooney Amanda M, van der Meulen Marjolein C H
Nancy E. and Peter C. Meinig School of Biomedical Engineering, Cornell University, Ithaca, New York.
Sibley School of Mechanical and Aerospace Engineering, Cornell University, Ithaca, New York.
Ann N Y Acad Sci. 2017 Dec;1410(1):85-92. doi: 10.1111/nyas.13523. Epub 2017 Nov 17.
Estrogen signaling and mechanical loading have individual and combined effects on skeletal maintenance and adaptation. Previous work investigating estrogen signaling both in vitro and in vivo using global estrogen receptor α (ERα) gene knockout mouse models has provided information regarding the role of ERα in regulating bone mass and adaptation to mechanical stimulation. However, these models have inherent limitations that confound interpretation of the data. Therefore, recent studies have focused on mice with targeted deletion of ERα from specific bone cells and their precursors. Cell stage, tissue type, and mouse sex all influence the effects of ERα gene deletion. Lack of ERα in osteoblast progenitor and precursor cells generally affects the periosteum of female and male mice. The absence of ERα in differentiated osteoblasts, osteocytes, and osteoclasts in mice generally resulted in reduced cancellous bone mass, with differing reports of the effect by animal sex and greater deficiencies in bone mass typically occurring in cancellous bone in female mice. Limited data exist for the role of bone cell-specific ERα in skeletal adaptation in vivo. Cell-specific ERα gene knockout mice provide an excellent platform for investigating the function of ERα in regulating skeletal phenotype and response to mechanical loading by sex and age.
雌激素信号传导和机械负荷对骨骼维持和适应性具有单独和联合作用。先前使用全球雌激素受体α（ERα）基因敲除小鼠模型在体外和体内研究雌激素信号传导的工作，提供了有关ERα在调节骨量和对机械刺激适应性方面作用的信息。然而，这些模型存在固有局限性，混淆了数据的解释。因此，最近的研究集中在从特定骨细胞及其前体中靶向缺失ERα的小鼠上。细胞阶段、组织类型和小鼠性别都会影响ERα基因缺失的效果。成骨细胞祖细胞和前体细胞中缺乏ERα通常会影响雌性和雄性小鼠的骨膜。小鼠分化的成骨细胞、骨细胞和破骨细胞中缺乏ERα通常会导致松质骨量减少，关于动物性别影响的报道各异，且雌性小鼠松质骨中的骨量缺陷通常更大。关于骨细胞特异性ERα在体内骨骼适应性中的作用的数据有限。细胞特异性ERα基因敲除小鼠为研究ERα在按性别和年龄调节骨骼表型及对机械负荷反应中的功能提供了一个极好的平台。
