The Role of Estrogen Receptor α in Response to Longitudinal Bone Growth in ob/ob Mice

Abstract

The absence of leptin results in contrasting growth pattern of appendicular and axial bone growth in ob/ob mice. Endochondral bone formation is an important procedure of growth plate determining the bone growth, where this procedure is also regulated by estrogen and its receptor (ER) signaling pathway. The present study is undertaken to explore the roles of ERs in regulating the different growth patterns in ob/ob mice. In this study, C57BL/6 female mice were used as wild-type (WT) mice; ob/ob mice and WT mice were age-matched fed, and bone length is analyzed by X-ray plain film at the 12 weeks old. We confirm that ob/ob mice have shorter femoral length and longer spine length than WT mice (p < 0.05). The contrasting expression patterns of chondrocyte proliferation proteins and hypertrophic marker proteins are also observed from the femur and spinal growth plate of ob/ob mice compared with WT mice (p < 0.01). Spearman’s analysis showed that body length (axial and appendicular length) is positively related to the expression level of ERα in growth plate. Three-week-old female ob/ob mice are randomized divided into three groups: 1) ob/ob + ctrl, 2) ob/ob + ERα antagonist (MPP), and 3) ob/ob + ERβ antagonist (PHTPP). Age-matched C57BL/6 mice were also divided into three groups, same as the groups of ob/ob mice. MPP and PHTPP were administered by intraperitoneal injection for 6 weeks. However, the results of X-ray and H&E staining demonstrate that leptin deficiency seems to disturb the regulating effects of ER antagonists on longitudinal bone growth. These findings suggested that region-specific expression of ERα might be associated with contrasting phenotypes of axial and appendicular bone growth in ob/ob mice. However, ER signaling on longitudinal bone growth was blunted by leptin deficiency in ob/ob mice, and the underlying association between ERs and leptin needs to be explored in future work.

11‐Ethoxyviburtinal improves chronic restraint stress‐induced anxiety‐like behaviors in gender‐specific mice via PI3K/Akt and E2/ERβ signaling pathways

“…Validating the pathways: C57BL/6J mice, half male and half female, were divided into the control group, CRS group, 11‐eth group (11‐ethoxyviburtinal, 2.0 mg/kg/d), 11‐eth + PHTPP group (11‐ethoxyviburtinal, 2.0 mg/kg/d; PHTPP, 0.3 mg/kg/d), 11‐eth + letrozole group (11‐ethoxyviburtinal, 2.0 mg/kg/d; letrozole, 1.0 mg/kg/d; Chaiton et al, 2019; Jin et al, 2021). We did not have a positive control group, because diazepam is the most commonly used drug as a positive control for anxiety disorders, whose anxiolytic mechanism is mainly through GABA signaling pathway.…”

Crosstalk between bone and other organs

“…On the one hand, leptin regulates appetite, energy expenditure and fertility regulated by brain. On the other hand, leptin links to bone remodeling: mice deficient in leptin ( ob/ob ) or its receptor ( db / db ) display a low bone mass phenotype [ 88 , 89 ]. The function of leptin in bone formation through the hypothalamus reveals completely opposite effects.…”