Estrogen-induced osteogenesis in intact female mice lacking ERβ

Abstract

We recently found that estrogen receptor (ER) antagonists prevent highdose estrogen from inducing the formation of new cancellous bone within the medullary cavity of mouse long bones. In the present investigation, we studied the role of specific ER subtypes in this response by examining whether this is impaired in female ER␤ Ϫ/Ϫ mice previously generated by targeted gene deletion. Vehicle or 17␤-estradiol (E 2) (range 4-4,000 g ⅐ kg Ϫ1 ⅐ day Ϫ1 ) was administered to intact female ER␤ Ϫ/Ϫ mice and wild-type littermates by subcutaneous injection for 28 days. The osteogenic response was subsequently assessed by histomorphometry performed on longitudinal and cross sections of the tibia. E 2 was found to cause an equivalent increase in cancellous bone formation in ER␤ Ϫ/Ϫ mice and littermate controls, as assessed at the proximal and distal regions of the proximal tibial metaphysis. E 2 also resulted in a similar increase in endosteal mineral apposition rate in these two genotypes, as assessed at the tibial diaphysis. In contrast, cortical area in ER␤ Ϫ/Ϫ mice was found to be greater than that in wild types irrespective of E 2 treatment, as was tibial bone mineral density as measured by dual-energy X-ray absorptiometry, consistent with previous reports of increased cortical bone mass in these animals. We conclude that, although ER␤ acts as a negative modulator of cortical modeling, this isoform does not appear to contribute to high-dose estrogen's ability to induce new cancellous bone formation in mouse long bones.osteoblasts; estrogen receptor; histomorphometry ESTROGEN EXERTS an important protective effect on the skeleton, as illustrated by the significant bone loss associated with estrogen deficiency (17), which is prevented by hormone replacement (8,24). This ability of estrogen to prevent bone loss is thought to reflect two distinct actions. First, numerous clinical and animal studies indicate that estrogen acts to suppress osteoclastic bone resorption, leading to a decrease in bone turnover (7,23,32). In addition, estrogen has been reported to stimulate osteoblast function when administered at a relatively high dose, as assessed in studies of postmenopausal women receiving estradiol implants (9, 26) and in rodent models (2, 6). Although higher doses of estrogen are associated with extraskeletal effects that may limit their use in postmenopausal women, improved understanding of the molecular basis for estrogen's actions on bone may provide the basis for developing novel therapeutic agents capable of targeting these.

A protective effect of Curcuma comosa Roxb. on bone loss in estrogen deficient mice

“…The finding that the bone protective effect of C. comosa is mediated through ER␣ is in agreement with the previous study showing that bone formation stimulated by estrogen requires the presence of ER␣ (McDougall et al, 2003). In addition, McDougall et al demonstrated in ER␤ -/− mice that ER␤ did not mediate the osteogenic response to estrogen (McDougall et al, 2002). However, the molecular mechanism by which diarylheptanoid compounds protect bone mass requires further studies.…”

Inhibin A Is an Endocrine Stimulator of Bone Mass and Strength

“…It is well documented that physiological estrogens suppress bone turnover but that high-dose estrogen treatment increases bone formation and is strongly anabolic (65)(66)(67). Similarly, it is also well accepted that glucocorticoids increase osteoblastogenesis in vitro (68 -73), whereas continuous in vivo exposure decreases osteoblastogenesis, increases osteoblast apoptosis, and increases osteoclast activity leading to bone loss (38, 74 -78).…”

Mice with a Disruption of the Imprinted Grb10 Gene Exhibit Altered Body Composition, Glucose Homeostasis, and Insulin Signaling during Postnatal Life

“…Adult mice killed by cervical dislocation were analyzed by dual-energy-X-ray absorptiometry (DXA) using a PIXImis scanner (Lunar, Madison, WI) with small-animal software, as previously described (40). The parameters that were evaluated included total area, lean tissue weight, and fat tissue weight.…”