scholarly journals Estrogen Receptor-α Dependency of Estrogen’s Stimulatory Action on Cancellous Bone Formation in Male Mice

Endocrinology ◽  
2003 ◽  
Vol 144 (5) ◽  
pp. 1994-1999 ◽  
Author(s):  
Kathleen E. McDougall ◽  
Mark J. Perry ◽  
Rachel L. Gibson ◽  
Shane M. Colley ◽  
Kenneth S. Korach ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Bone Formation ◽  
Cancellous Bone ◽  
Bone Marrow Cells ◽  
Significant Proportion ◽  
Activation Function ◽  
Mineral Apposition Rate ◽  
Long Bones ◽  
Male Mice ◽  
Stimulatory Action

We examined whether estrogen receptor (ER)α is required for estrogen to stimulate cancellous bone formation in long bones of male mice. 17β-Estradiol (E2) was administered to ERα−/− male mice or wild-type (WT) littermate controls at 40, 400, or 4000 μg/kg by daily sc injection for 28 d and histomorphometric analysis performed at the distal femoral metaphysis. In WT mice, treatment with E2 (40 μg/kg·d) increased the proportion of cancellous bone surfaces undergoing mineralization and stimulated mineral apposition rate. In addition, higher doses of E2 induced the formation of new cancellous bone formation surfaces in WT mice. In contrast, E2 had little effect on any of these parameters in ERα−/− mice. Immunohistochemistry was subsequently performed using an ERα-specific C-terminal polyclonal antibody. In WT mice, ERα was expressed both by cancellous osteoblasts and a significant proportion of mononuclear bone marrow cells. Immunoreactivity was also observed in cancellous osteoblasts of ERα−/− mice, resulting from expression of the activation function-1-deficient 46-kDa ERα isoform previously reported to be expressed in normal osteoblasts and bones of ERα−/− mice. Taken together, our results suggest that estrogen stimulates bone formation in mouse long bones via a mechanism that requires the presence of full-length ERα possessing activation function-1.

Estrogen-induced osteogenesis in intact female mice lacking ERβ

2002 ◽  
Vol 283 (4) ◽  
pp. E817-E823 ◽  
Author(s):  
K. E. McDougall ◽  
M. J. Perry ◽  
R. L. Gibson ◽  
J. M. Bright ◽  
S. M. Colley ◽  
...  
Keyword(s):  
Bone Formation ◽  
Cancellous Bone ◽  
Cross Sections ◽  
Mineral Apposition Rate ◽  
High Dose ◽  
Long Bones ◽  
Mineral Density ◽  
Intact Female ◽  
Targeted Gene Deletion ◽  
Osteogenic Response

We recently found that estrogen receptor (ER) antagonists prevent high-dose 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 ERβ−/− mice previously generated by targeted gene deletion. Vehicle or 17β-estradiol (E2) (range 4–4,000 μg · kg−1 · day−1) was administered to intact female ERβ−/− 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. E2 was found to cause an equivalent increase in cancellous bone formation in ERβ−/− mice and littermate controls, as assessed at the proximal and distal regions of the proximal tibial metaphysis. E2 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 ERβ−/− mice was found to be greater than that in wild types irrespective of E2 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 ERβ 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.

High bone mass gained by exercise in growing male mice is increased by subsequent reduced exercise

2004 ◽  
Vol 97 (3) ◽  
pp. 806-810 ◽  
Author(s):  
Jian Wu ◽  
Xin Xiang Wang ◽  
Mitsuru Higuchi ◽  
Kazuhiko Yamada ◽  
Yoshiko Ishimi
Keyword(s):  
Bone Mineral Density ◽  
Bone Formation ◽  
Bone Mass ◽  
Exercise Group ◽  
Mineral Apposition Rate ◽  
Male Mice ◽  
Sedentary Control ◽  
Mineral Density ◽  
High Bone Mass ◽  
High Bone

Exercise-induced bone gains are lost if exercise ceases. Therefore, continued exercise at a reduced frequency or intensity may be required to maintain these benefits. In this study, we evaluated whether 4 wk of reduced exercise after 4 wk of running exercise in growing male mice results in the maintenance of high bone mass. Five-week-old mice were divided into the following groups: 1) baseline control; 2) 4-wk control; 3) 4-wk exercise; 4) 8-wk control; 5) 4-wk exercise followed by 4-wk cessation of training; and 6) 4-wk exercise followed by reduced exercise at half the frequency. The regimen consisted of exercise 6 days/wk, and the reduced exercise regimen consisted of running 3 days/wk on a treadmill for 30 min/day, at 12 m/min on a 10° uphill slope. Running exercise significantly increased bone mineral density of the femur, periosteal mineral apposition rate, bone formation rate, percent labeled perimeter at the midfemur, and osteogenic activity of bone marrow cells. However, these parameters declined to the age-matched sedentary control after cessation of training. In contrast, the reduced exercise group had significantly higher mineral apposition rate compared with those of the sedentary control and cessation of training groups. Furthermore, bone mineral density for the reduced exercise group was significantly higher than those for the other groups. These results suggest that the high bone formation gained through exercise can be maintained, and bone mass was further increased by subsequent exercise even if the exercise frequency is reduced.

scholarly journals Tamoxifen Stimulates Cancellous Bone Formation in Long Bones of Female Mice

Endocrinology ◽  
2005 ◽  
Vol 146 (3) ◽  
pp. 1060-1065 ◽  
Author(s):  
M. J. Perry ◽  
S. Gujra ◽  
T. Whitworth ◽  
J. H. Tobias
Keyword(s):  
Bone Formation ◽  
Protective Effect ◽  
Cancellous Bone ◽  
Bone Growth ◽  
Similar Response ◽  
Stimulatory Action ◽  
Female Mice ◽  
Estrogen Receptor Modulators ◽  
Osteoblast Activity ◽  
17Β Estradiol

Selective estrogen receptor modulators (SERMs) have been developed as a means of targeting estrogen’s protective effect on the skeleton in the treatment of postmenopausal osteoporosis. Although it is well established that SERMs such as tamoxifen inhibit bone resorption in a similar manner to estrogen, whether this agent shares estrogen’s stimulatory action on bone formation is currently unclear. To address this question, we compared the effect of treatment for 28 d with 17β-estradiol (E2; 0.1, 1.0 mg/kg·d) and tamoxifen (0.1, 1.0, or 10 mg/kg·d) on cancellous bone formation at the proximal tibial metaphysis of intact female mice. E2 stimulated the formation of new cancellous bone throughout the metaphysis. A similar response was observed after administration of tamoxifen, the magnitude of which was approximately 50% of that seen after E2. As expected, E2 was found to suppress longitudinal bone growth, but in contrast, this parameter was stimulated by tamoxifen. We conclude that tamoxifen acts as an agonist with respect to estrogen’s stimulatory action on bone formation but as an antagonist in terms of estrogen’s inhibition of longitudinal growth, suggesting that the protective effect of SERMs on the skeleton is partly mediated by stimulation of osteoblast activity.

scholarly journals Global estrogen receptor-α knockout has differential effects on cortical and cancellous bone in aged male mice

FACETS ◽  
2020 ◽  
Vol 5 (1) ◽  
pp. 328-348
Author(s):  
Rebecca K. Dirkes ◽  
Nathan C. Winn ◽  
Thomas J. Jurrissen ◽  
Dennis B. Lubahn ◽  
Victoria J. Vieira-Potter ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Cancellous Bone ◽  
Lumbar Vertebrae ◽  
Estrogen Receptor Α ◽  
Femoral Diaphysis ◽  
Male Mice ◽  
Micro Computed Tomography ◽  
Trabecular Microarchitecture ◽  
Skeletal Site ◽  
Trabecular Number

Estrogen receptor-α knockout (ERKO) in female rodents results in bone loss associated with increased osteocyte sclerostin expression; whether this also occurs in males is unknown. Here, we examined the effects of ERKO on femoral cortical geometry, trabecular microarchitecture, and osteocyte sclerostin expression of the femur and lumbar vertebrae. At 14 months of age, male ERKO and wild-type (WT) littermates ( n = 6 per group) were sacrificed, and femora and vertebra were collected. Cortical geometry and trabecular microarchitecture were assessed via micro-computed tomography; osteocyte sclerostin expression was assessed via immunohistochemistry. ANCOVA with body weight was used to compare ERKO and WT for cortical geometry; t-tests were used for all other outcomes. Regardless of skeletal site, ERKO mice had greater trabecular bone volume and trabecular number and decreased trabecular separation compared with WT. In the femoral diaphysis, ERKO had lower total area, cortical area, and cortical thickness compared with WT. The percentage of sclerostin+ osteocytes was increased in ERKO animals in cortical bone but not in cancellous bone of the femur or the lumbar vertebrae. In conclusion, ERKO improved trabecular microarchitecture in aged male mice, but negatively altered femoral cortical geometry associated with a trend towards increased cortical sclerostin expression.

scholarly journals Differential effects of systemic prostaglandin E2 on bone mass in rat long bones and calvariae

1998 ◽  
Vol 156 (1) ◽  
pp. 51-57 ◽  
Author(s):  
I Suponitzky ◽  
M Weinreb
Keyword(s):  
Bone Formation ◽  
Bone Mass ◽  
Prostaglandin E2 ◽  
Body Weight Gain ◽  
Compact Bone ◽  
Mineral Apposition Rate ◽  
Long Bones ◽  
Bone Area ◽  
Marrow Cavity

Prostaglandin E2 (PGE2) has been shown to possess anabolic properties when administered systemically. All the experiments performed so far examined long bones from animals of varying age and bone status. In this study we compared the changes in bone mass of long bones (femur, tibia and humerus) to those in calvariae after a 3-week daily administration of 6 mg/kg PGE2 into 3-week-old rats. This regimen inhibited body weight gain (by 14.1%) as well as longitudinal growth of long bones (by 2.2-3.5%) but increased their mass. Ash weight (measuring both cancellous and compact bone) increased by 10.1-14.1% but tibial cancellous bone area was elevated by 54%. Radial growth was slightly reduced due to transient inhibition of mineral apposition rate at the periosteal envelope but the expansion of the marrow cavity was inhibited to a greater extent, resulting in an 8.1% increase in the relative compact bone area. The increased bone mass was associated with greater mechanical strength of the femoral neck (24.2% increase in fracture load and 19% in stiffness). In contrast, PGE2 administration did not affect calvarial thickness or mineral apposition rate but increased its density, i.e. reduced the area of marrow spaces due to stimulation of endocortical bone formation at this site. The pattern of bone mass changes documented in this study closely correlates with that of the induced expression of early-response genes following a single dose of PGE2 as we recently reported. These data, therefore, support the hypothesis that in vivo administration of an anabolic dose of PGE2 increases bone formation and augments bone mass largely by stimulating the recruitment of new osteoblasts via induction of the proliferation and/or differentiation of bone marrow osteogenic precursors.

Disuse in adult male rats attenuates the bone anabolic response to a therapeutic dose of parathyroid hormone

2006 ◽  
Vol 101 (3) ◽  
pp. 881-886 ◽  
Author(s):  
Russell T. Turner ◽  
Sutada Lotinun ◽  
Theresa E. Hefferan ◽  
Emily Morey-Holton
Keyword(s):  
Parathyroid Hormone ◽  
Bone Formation ◽  
Cancellous Bone ◽  
Therapeutic Dose ◽  
Weight Bearing ◽  
Formation Rate ◽  
Hindlimb Unloading ◽  
Male Rats ◽  
Mineral Apposition Rate ◽  
Bone Formation Rate

Intermittent treatment with parathyroid hormone (PTH) increases bone formation and prevents bone loss in hindlimb-unloaded (HLU) rats. However, the mechanisms of action of PTH are incompletely known. To explore possible interactions between weight bearing and PTH, we treated 6-mo-old weight-bearing and HLU rats with a human therapeutic dose (1 μg·kg−1·day−1) of human PTH(1–34) (hPTH). Cortical and cancellous bone formation was measured in tibia at the diaphysis proximal to the tibia-fibula synostosis and at the proximal metaphysis, respectively. Two weeks of hindlimb unloading resulted in a dramatic decrease in the rate of bone formation at both skeletal sites, which was prevented by PTH treatment at the cancellous site only. In contrast, PTH treatment increased cortical as well as cancellous bone formation in weight-bearing rats. Two-way ANOVA revealed that hPTH and HLU had independent and opposite effects on all histomorphometric indexes of bone formation [mineral apposition rate (MAR), double-labeled perimeter (dLPm), and bone formation rate (BFR)] at both skeletal sites. The bone anabolic effects of weight bearing and hPTH on dLPm and BFR at the cortical site were additive, as were the effects on MAR at the cancellous site. In contrast, weight bearing and hPTH resulted in synergistic increases in cortical bone MAR and cancellous bone dLPm and BFR. We conclude that weight bearing and PTH act cooperatively to increase bone formation by resulting in site-specific additive and synergistic increases in indexes of osteoblast number and activity, suggesting that weight-bearing exercise targeted to osteopenic skeletal sites may improve the efficacy of PTH therapy for osteoporosis.

scholarly journals Estrogen receptor-  in osteocytes is important for trabecular bone formation in male mice

2013 ◽  
Vol 110 (6) ◽  
pp. 2294-2299 ◽  
Author(s):  
S. H. Windahl ◽  
A. E. Borjesson ◽  
H. H. Farman ◽  
C. Engdahl ◽  
S. Moverare-Skrtic ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Bone Formation ◽  
Trabecular Bone ◽  
Male Mice

1625: Role of Estrogen Receptor β in the Regulation of Sexual Behavior in Male Mice

2004 ◽  
Vol 171 (4S) ◽  
pp. 429-429
Author(s):  
Masayoshi Nomura ◽  
Naohiro Fujimoto ◽  
Donald W. Pfaff ◽  
Sonoko Ogawa ◽  
Tetsuro Matsumoto
Keyword(s):  
Estrogen Receptor ◽  
Sexual Behavior ◽  
Estrogen Receptor Β ◽  
Male Mice

Dietary Calcium Supplementation Suppresses Bone Formation in Magnesium-Deficient Rats

2006 ◽  
Vol 76 (3) ◽  
pp. 111-116 ◽  
Author(s):  
Hiroshi Matsuzaki ◽  
Misao Miwa
Keyword(s):  
Bone Formation ◽  
Calcium Supplementation ◽  
Control Diet ◽  
Formation Rate ◽  
Dietary Calcium ◽  
Mineral Apposition Rate ◽  
Control Group ◽  
Deficient Diet ◽  
Bone Formation Rate ◽  
Male Wistar Rats

The purpose of this study was to clarify the effects of dietary calcium (Ca) supplementation on bone metabolism of magnesium (Mg)-deficient rats. Male Wistar rats were randomized by weight into three groups, and fed a control diet (control group), a Mg-deficient diet (Mg- group) or a Mg-deficient diet having twice the control Ca concentrations (Mg-2Ca group) for 14 days. Trabecular bone volume was significantly lower in the Mg - and Mg-2Ca groups than in the control group. Trabecular number was also significantly lower in the Mg - and Mg-2Ca groups than in the control group. Mineralizing bone surface, mineral apposition rate (MAR), and surface referent bone formation rate (BFR/BS) were significantly lower in the Mg - and Mg-2Ca groups than in the control group. Furthermore, MAR and BFR/BS were significantly lower in the Mg-2Ca group than in the Mg - group. These results suggest that dietary Ca supplementation suppresses bone formation in Mg-deficient rats.

Extranuclear effects of estrogen on cortical bone in males is dependent on estrogen receptor A activation function-1

2016 ◽  
Author(s):  
Helen Farman ◽  
Jianyao Wu ◽  
Karin Gustafsson ◽  
Sara Windahl ◽  
Sung Kim ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Cortical Bone ◽  
Activation Function
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