Deletion of Dickkopf-1 in osteoblasts or osteocytes increases bone volume in female mice

2016 ◽  
Author(s):  
Sylvia Thiele ◽  
Ulrike Baschant ◽  
Stefanie Thiele ◽  
Christof Niehrs ◽  
Lynda Bonewald ◽  
...  
Keyword(s):  
Bone Volume ◽  
Female Mice ◽  
Dickkopf 1

scholarly journals Postnatal Skeletal Deletion of Dickkopf-1 Increases Bone Formation and Bone Volume in Male and Female Mice, Despite Increased Sclerostin Expression

2018 ◽  
Vol 33 (9) ◽  
pp. 1698-1707 ◽  
Author(s):  
Juliane Colditz ◽  
Sylvia Thiele ◽  
Ulrike Baschant ◽  
Christof Niehrs ◽  
Lynda F Bonewald ◽  
...  
Keyword(s):  
Bone Formation ◽  
Bone Volume ◽  
Male And Female ◽  
Female Mice ◽  
Dickkopf 1

scholarly journals Dickkopf-1 blocks 17β-estradiol-enhanced object memory consolidation in ovariectomized female mice

2019 ◽  
Vol 114 ◽  
pp. 104545 ◽  
Author(s):  
Lisa R. Taxier ◽  
Sarah M. Philippi ◽  
Ashley M. Fortress ◽  
Karyn M. Frick
Keyword(s):  
Memory Consolidation ◽  
Object Memory ◽  
Female Mice ◽  
17Β Estradiol ◽  
Dickkopf 1

scholarly journals Mechanical Loading-Related Bone Gain Is Enhanced by Tamoxifen but Unaffected by Fulvestrant in Female Mice

Endocrinology ◽  
2010 ◽  
Vol 151 (12) ◽  
pp. 5582-5590 ◽  
Author(s):  
Toshihiro Sugiyama ◽  
Gabriel L. Galea ◽  
Lance E. Lanyon ◽  
Joanna S. Price
Keyword(s):  
Trabecular Bone ◽  
Cortical Bone ◽  
Mechanical Loading ◽  
Bone Volume ◽  
Trabecular Bone Volume ◽  
Trabecular Thickness ◽  
Female Mice ◽  
Short Period ◽  
Bone Gain ◽  
The Right

Accumulating evidence indicates that estrogen receptors (ERs) are involved in the mechano-adaptive mechanisms by which loading influences the mass and architecture of bones to establish and maintain their structural load-bearing competence. In the present study, we assessed the effects of the ER modulators tamoxifen and fulvestrant (ICI 182,780) on loading-related changes in the volume and structure of trabecular and cortical bone in the tibiae of female mice. Ten days after actual or sham ovariectomy, 17-wk-old female C57BL/6 mice were treated with vehicle (peanut oil), tamoxifen (0.02, 0.2, or 2 mg/kg · d), fulvestrant (4 mg/kg · d), or their combination and the right tibiae subjected to a short period of noninvasive axial loading (40 cycles/d) on 5 d during the subsequent 2 wk. In the left control tibiae, ovariectomy, tamoxifen, or fulvestrant did not have any significant effect on cortical bone volume, whereas trabecular bone volume was decreased by ovariectomy, increased by tamoxifen, and unaffected by fulvestrant. In the right tibiae, loading was associated with increases in both trabecular and cortical bone volume. Notably, the medium dose of tamoxifen synergistically enhanced loading-related gain in trabecular bone volume through an increase in trabecular thickness. Fulvestrant had no influence on the effects of loading but abrogated the enhancement of loading-related bone gain by tamoxifen. These data demonstrate that, at least in female mice, the adaptive response to mechanical loading of trabecular bone can be enhanced by ER modulators, in this case by tamoxifen.

scholarly journals The Role of Dickkopf-1 in Thyroid Hormone–Induced Changes of Bone Remodeling in Male Mice

Endocrinology ◽  
2019 ◽  
Vol 160 (3) ◽  
pp. 664-674 ◽  
Author(s):  
Elena Tsourdi ◽  
Juliane Colditz ◽  
Franziska Lademann ◽  
Eddy Rijntjes ◽  
Josef Köhrle ◽  
...  
Keyword(s):  
Thyroid Hormone ◽  
Bone Mass ◽  
Bone Turnover ◽  
Knockout Mice ◽  
Bone Volume ◽  
Bone Homeostasis ◽  
Male Mice ◽  
Induced Changes ◽  
Dickkopf 1

Abstract Thyroid hormones regulate bone homeostasis, and exogenously induced hyperthyroidism and hypothyroidism in mice was recently found to be associated with an altered expression of the Wnt inhibitor Dickkopf-1 (Dkk1), a determinant of bone mass. Here, we assessed the role of Dkk1 in thyroid hormone–induced changes in bone using conditional Dkk1 knockout mice. Male mice with a global (Dkk1fl/fl;Rosa26-CreERT2) or osteocyte-specific (Dkk1fl/fl;Dmp1:Cre) deletion of Dkk1 were pharmacologically rendered hypothyroid or hyperthyroid. The bone phenotype was analyzed using micro-CT analysis, dynamic histomorphometry, and serum concentrations of bone turnover markers. Hypothyroid and hyperthyroid Cre-negative mice of either Cre line revealed the expected changes in bone volume with hypothyroid mice displaying a 40% to 60% increase in vertebral trabecular bone volume, while hyperthyroid mice lost 45% to 60% of bone volume. Similar changes were observed at the spine. Interestingly, Cre-positive mice of both lines did not gain or lose as much bone at the femur when rendered hypothyroid or hyperthyroid. While Cre-negative hypothyroid mice gained 80% to 100% bone volume, Cre-positive hypothyroid mice only increased their bone volume by 55% to 90%. Similarly, Cre-negative hyperthyroid mice lost 74% to 79% bone, while Cre-positive hyperthyroid mice merely lost 40% to 54%. Despite these site-specific differences, both global and osteocyte-specific Dkk1 knockout mice displayed similar changes in bone turnover as their Cre-negative controls in the hypothyroid and hyperthyroid states. While osteoblast and osteoclast parameters were increased in hyperthyroidism, hypothyroidism potently suppressed bone cell activities. Loss of Dkk1 is not sufficient to fully reverse thyroid hormone–induced changes in bone mass and bone turnover.

scholarly journals Role of Osteoblast Gi Signaling in Age-Related Bone Loss in Female Mice

Endocrinology ◽  
2017 ◽  
Vol 158 (6) ◽  
pp. 1715-1726 ◽  
Author(s):  
Susan M. Millard ◽  
Liping Wang ◽  
Lalita Wattanachanya ◽  
Dylan O’Carroll ◽  
Aaron J. Fields ◽  
...  
Keyword(s):  
Bone Loss ◽  
Bone Formation ◽  
Bending Strength ◽  
The Elderly ◽  
Bone Volume ◽  
Littermate Control ◽  
Female Mice ◽  
Age Related ◽  
Aging Women ◽  
G Protein Coupled

Abstract Age-related bone loss is an important risk factor for fractures in the elderly; it results from an imbalance in bone remodeling mainly due to decreased bone formation. We have previously demonstrated that endogenous G protein–coupled receptor (GPCR)-driven Gi signaling in osteoblasts (Obs) restrains bone formation in mice during growth. Here, we launched a longitudinal study to test the hypothesis that Gi signaling in Obs restrains bone formation in aging mice, thereby promoting bone loss. Our approach was to block Gi signaling in maturing Obs by the induced expression of the catalytic subunit of pertussis toxin (PTX) after the achievement of peak bone mass. In contrast to the progressive cancellous bone loss seen in aging sex-matched littermate control mice, aging female Col1(2.3)+/PTX+ mice showed an age-related increase in bone volume. Increased bone volume was associated with increased bone formation at both trabecular and endocortical surfaces as well as increased bending strength of the femoral middiaphyses. In contrast, male Col1(2.3)+/PTX+ mice were not protected from age-related bone loss. Our results indicate that Gi signaling markedly restrains bone formation at cancellous and endosteal bone surfaces in female mice during aging. Blockade of the relevant Gi-coupled GPCRs represents an approach for the development of osteoporosis therapies—at least in the long bones of aging women.

Central forebrain Fos responses to familiar male odours are attenuated in recently mated female mice

2001 ◽  
Vol 13 (2) ◽  
pp. 389-399 ◽  
Author(s):  
Heather A. Halem ◽  
James A. Cherry ◽  
Michael J. Baum
Keyword(s):  
Female Mice ◽  
Mated Female

18F-sodium fluoride bone deposition quantitation with PET in Mice: Variation with age, sex, and circadian rhythm

2020 ◽  
Vol 59 (06) ◽  
pp. 428-437
Author(s):  
Viktoria Dorau-Rutke ◽  
Kai Huang ◽  
Mathias Lukas ◽  
Marc O. Schulze ◽  
Christian Rosner ◽  
...  
Keyword(s):  
Circadian Rhythm ◽  
Sodium Fluoride ◽  
Bone Growth ◽  
Bone Volume ◽  
Sleep Phase ◽  
Median Percentage ◽  
Bone Uptake ◽  
Pooled Data ◽  
Uptake Studies ◽  
Bone Deposition

Abstract Aim The aim of this study was to establish a data base for normal 18F-sodium fluoride (18F-NaF) bone uptake as a function of age, sex and circadian rhythm in mice. Methods In 12 female (F) and 12 male (M) C57BL/6N mice PET images were acquired 90 min after intravenous injection of 20 MBq 18F-NaF for 30 minutes. Each mouse was imaged in follow-up studies at 1, 3, 6, 13 and 21 months of age. In order to assess for physiologic changes related to circadian rhythm, animals were imaged during light (sleep phase) as well as during night conditions (awake phase). Bone uptake is described as the median percentage of the injected activity (%IA) and in relation to bone volume (%IA/ml). Results A significant smaller bone volume was found in F (1.79 ml) compared to M (1.99 ml; p < 0.001). In sex-pooled data, highest bone uptake occurred at an age of 1 month (61.1 %IA, 44.5 %IA/ml) with a significant reduction (p < 0.001) at age 3 months (43.6 %IA, 23.6 %IA/ml), followed by an increase between 13 (47.3 %IA, 24.5 %IA/ml) and 21 months (52.2 %IA, 28.1 %IA/ml). F had a significantly higher total uptake (F 48.2 %IA, M 43.8 %IA; p = 0.026) as well as a higher uptake per ml bone tissue (F 27.0 %IA/ml; M 22.4 %IA/ml; p < 0.001). A significant impact of circadian rhythm was only found for F at ages of 3 and 6 months with a higher uptake during the sleep phase. Conclusion Circadian rhythm had a significant impact on uptake only in F of 3 and 6 months. Regarding sex, F showed generally higher uptake rates than M. The highest uptake values were observed during bone growth at age 1 month in both sexes, a second uptake peak occurred in elderly F. Designing future bone uptake studies with M, attention must be paid to age only, while in F circadian rhythm and age must be taken into account.

A subchronic oral toxicity study on medical herb extract, KIOM CRC#BP10A, in male and female mice

Planta Medica ◽  
2015 ◽  
Vol 81 (16) ◽  
Author(s):  
ES Cho ◽  
YJ Lee ◽  
JS Park ◽  
J Kim ◽  
NS Kim ◽  
...  
Keyword(s):  
Toxicity Study ◽  
Oral Toxicity ◽  
Male And Female ◽  
Female Mice ◽  
Subchronic Oral Toxicity Study ◽  
Herb Extract
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