Osteoprotective Effects of Estrogen in the Maxillary Bone Depend on ERα

Abstract

Estrogen deficiency results in disruption of maxillary alveolar bone microarchitecture. Most of the actions of estrogen in long bones occur via estrogen receptor α (ERα). However, the function of ERα in the maxillary bone has not been defined. We aimed to investigate the role and underlying mechanisms of ERα in the physiological and mechanically induced alveolar bone remodeling in female and male mice. Wild-type (WT) and ERα(-/-) (ERKOα) mice were subjected to mechanically stimulated bone remodeling by inducing orthodontic tooth movement (OTM). The maxillary bone was analyzed using histomorphometric analysis, micro-computed tomography, quantitative polymerase chain reaction, and energy-dispersive spectroscopy. Bone marrow cells (BMCs) from WT and ERKOα mice were tested for their capacity to differentiate into osteoblasts and osteoclasts. Both male and female ERKOα mice exhibited marked reduction of alveolar bone mass and increased OTM. This response was associated with an increased number of osteoclasts and reduced number of apoptotic cells and osteoblasts in the periodontium and alveolar bone. Consistently, ERKOα mice exhibited lower levels of calcium in bone and increased expression of IL-33 (interleukin-33), TNF-α (tumor necrosis factor α), and IL-1β (interleukin-1β) and decreased expression of dentin matrix acidic phosphoprotein and alkaline phosphatase in periodontal tissues. Moreover, the differentiation of osteoclasts and osteoblasts in vitro was significantly higher in BMCs obtained from ERKOα. ERα is required to maintain the microarchitecture of maxillary alveolar bone. This process is linked to bone cell differentiation and apoptosis, as well as local production of inflammatory molecules such as IL-33, TNF-α, and IL-1β.

ST2 regulates bone loss in a site‐dependent and estrogen‐dependent manner

“…Moreover, there are multiple mechanisms for estrogen effects on bone cells, such as a blockade of osteoclast differentiation and activation, and an increase in the rate of apoptosis . We observed that the OTM and osteoclast numbers were increased in both ST2 −/− and OVX WT mice, confirming the osteoprotective effects of IL‐33 and estrogen on alveolar bone remodeling . However, our findings showed that under the condition of estrogen deficiency, a similar amount of tooth movement was observed in ST2 −/− OVX mice compared with that in WT OVX and ST2 −/− ‐intact mice.…”

“…High‐resolution scans with an isotropic voxel size of 8.62 were acquired (50 kV, 0.5 mm aluminum filter, 0.5° rotation angle). Analyses of the bone mineral density (BMD), percentage of trabecular bone volume/total volume (BV/TV%), bone volume (BV), trabecular thickness (Tb.Th), trabecular separation (Tb.Sp), and trabecular number (Tb.N) were performed in the furcation area of the first molar root and the distal region of the femur, excluding the growth plate and vertebra (lumbar 1) …”

Orthognathic surgery during breast cancer treatment—A case report

“…Estrogen deficiency results in loss of maxillary bone [8], [9], and estrogen receptor α is required to maintain the microarchitecture of the maxillary alveolar bone [10]. Estrogen is also reported to be an important regulator of cartilage homeostasis, growth and maturation [11], and controls the growth and closure of the epiphyseal plate [12].…”

Icariin prevents oestrogen deficiency–induced alveolar bone loss through promoting osteogenesis via STAT3

“…Alveolar bone is an irregular protuberance of the jawbone that accommodates and provides adequate support for the teeth. A series of studies have indicated a decrease in alveolar bone density and quality in women with post‐menopausal osteoporosis . Our previous studies also indicated that oestrogen deficiency induces alveolar bone loss and trabecular fragmentation in rats .…”