Mouse models to evaluate the role of estrogen receptor α in skeletal maintenance and adaptation.
Amanda M RooneyMarjolein C H van der MeulenPublished in: Annals of the New York Academy of Sciences (2017)
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.
Keyphrases
- estrogen receptor
- bone mineral density
- bone loss
- soft tissue
- bone regeneration
- induced apoptosis
- single cell
- endoplasmic reticulum
- mouse model
- genome wide
- cell therapy
- breast cancer cells
- electronic health record
- healthcare
- postmenopausal women
- gene expression
- adipose tissue
- type diabetes
- copy number
- high throughput
- metabolic syndrome
- high fat diet induced
- machine learning
- stem cells
- big data
- oxidative stress
- endoplasmic reticulum stress
- deep learning
- bone marrow
- case control