scholarly journals Expression of estrogen receptors and enzymes involved in sex steroid metabolism in the rat tibia during sexual maturation

2004 ◽  
Vol 180 (3) ◽  
pp. 457-467 ◽  
Author(s):  
BC van der Eerden ◽  
CW Lowik ◽  
JM Wit ◽  
M Karperien
Keyword(s):  
Bone Mass ◽  
Sexual Maturation ◽  
Bone Cells ◽  
Male Rats ◽  
Steroid Metabolism ◽  
Sex Steroid ◽  
Type I ◽  
Beneficial Effects ◽  
Bone Mass Accrual ◽  
Er Alpha

Estrogens are essential for bone mass accrual but their role before sexual maturation has remained elusive. Using in situ hybridization and immunohistochemistry, we investigated the expression of both estrogen receptor (ER) alpha and beta mRNA and protein as well as several mRNAs coding for enzymes involved in sex steroid metabolism (aromatase, type I and II 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD), steroid sulfatase (STS) and type I 5 alpha-reductase) on sections of tibial metaphyses before (1- and 4-week-old), during (7-week-old) and after (16-week-old) sexual maturation in female and male rats. ER alpha and ER beta mRNA and protein were detected in metaphyseal bone in lining cells, osteoblasts, osteoclasts and some osteocytes with no apparent differences in expression during development or between the sexes. In contrast, aromatase, type I and II 17 beta-HSD and type I 5 alpha-reductase mRNAs were first detected in osteoblasts, osteoclasts and occasionally in osteocytes from sexual maturation (7-week-old rat) and onwards. Only STS was present before sexual maturation. To study the significance of ER alpha and beta expression in bone before sexual maturation when circulating sex steroid levels are low, 26-day-old female and male rats underwent gonadectomy or 17 beta-estradiol (E(2)) supplementation (0.5 mg/21 days) during 3 weeks. Following gonadectomy, trabecular bone volume (TBV) was lower in males (P=0.03) and there was a trend towards reduction in females (P=0.057). E(2) supplementation increased tibial TBV compared with controls in both genders as assessed by Masson-Goldner staining. These data suggest that the presence of ERs in bone cells before sex maturation might be of significance for bone mass accrual. Furthermore, based on the mRNA expression of the crucial enzymes aromatase and type I 17 beta-HSD, we suggest that bone cells in the tibial metaphysis acquire the intrinsic capacity to metabolize sex steroids from sexual maturation onwards. This process may contribute to the beneficial effects of estrogen on bone mass accrual, possibly by intracrinology.

scholarly journals Skeletal parasympathetic innervation communicates central IL-1 signals regulating bone mass accrual

2012 ◽  
Vol 109 (38) ◽  
pp. 15455-15460 ◽  
Author(s):  
Alon Bajayo ◽  
Arik Bar ◽  
Adam Denes ◽  
Marilyn Bachar ◽  
Vardit Kram ◽  
...  
Keyword(s):  
Nervous System ◽  
Bone Resorption ◽  
Bone Mass ◽  
Pseudorabies Virus ◽  
Parasympathetic Nervous System ◽  
Bone Cells ◽  
Low Bone Mass ◽  
Parasympathetic Innervation ◽  
Skeletal Mass ◽  
Bone Mass Accrual

Bone mass accrual is a major determinant of skeletal mass, governed by bone remodeling, which consists of bone resorption by osteoclasts and bone formation by osteoblasts. Bone mass accrual is inhibited by sympathetic signaling centrally regulated through activation of receptors for serotonin, leptin, and ACh. However, skeletal activity of the parasympathetic nervous system (PSNS) has not been reported at the bone level. Here we report skeletal immune-positive fibers for the PSNS marker vesicular ACh transporter (VAChT). Pseudorabies virus inoculated into the distal femoral metaphysis is identifiable in the sacral intermediolateral cell column and central autonomic nucleus, demonstrating PSNS femoral innervation originating in the spinal cord. The PSNS neurotransmitter ACh targets nicotinic (nAChRs), but not muscarinic receptors in bone cells, affecting mainly osteoclasts. nAChR agonists up-regulate osteoclast apoptosis and restrain bone resorption. Mice deficient of the α2nAChR subunit have increased bone resorption and low bone mass. Silencing of the IL-1 receptor signaling in the central nervous system by brain-specific overexpression of the human IL-1 receptor antagonist (hIL1raAst+/+ mice) leads to very low skeletal VAChT expression and ACh levels. These mice also exhibit increased bone resorption and low bone mass. In WT but not in hIL1raAst+/+ mice, the cholinergic ACh esterase inhibitor pyridostigmine increases ACh levels and bone mass apparently by inhibiting bone resorption. Taken together, these results identify a previously unexplored key central IL-1–parasympathetic–bone axis that antagonizes the skeletal sympathetic tone, thus potently favoring bone mass accrual.

scholarly journals Lack of dose-responsive effect of dietary phyto-oestrogens on transepithelial calcium transport in human intestinal-like Caco-2 cells

2004 ◽  
Vol 91 (1) ◽  
pp. 5-9 ◽  
Author(s):  
Alice A. Cotter ◽  
Kevin D. Cashman
Keyword(s):  
Bone Mass ◽  
Calcium Transport ◽  
Bone Cells ◽  
Cell Model ◽  
Reproductive Tissue ◽  
Direct Effects ◽  
Transcellular Transport ◽  
Beneficial Effects ◽  
Asian Populations ◽  
Dose Dependent

Ca absorption has been shown to be unaffected by high luminal concentrations of two commonly consumed soyabean phyto-oestrogens (PO) (genistein and daidzein) in Caco-2 cells grown under oestrogen-depleted conditions. However, these compounds exhibit dose-dependent biphasic effects in some tissues, such as reproductive tissue and bone. Thus, in light of this biphasic activity, the effect of lower concentrations of genistein and daidzein on Ca absorption requires further investigation. Therefore, the aim of the present study was to investigate the effect of a range of concentrations of genistein and daidzein on Ca absorption in the human Caco-2 intestinal-like cell model. Caco-2 cells were seeded onto permeable filter supports and allowed to differentiate into monolayers. On day 21, the Caco-2 monolayers (n 12 per treatment), grown in oestrogen-deplete media, were then exposed to 10 nm-1,25-dihydroxycholecalciferol (1,25 (OH)2D3), or 1, 10 and 50 μm-genistein or -daidzein for 24 h. After exposure, transepithelial and transcellular transport of 45Ca and fluorescein transport were measured. As expected, 1,25 (OH)2D3 stimulated Ca absorption in Caco-2 cells, by up regulating transcellular transport. Ca absorption was unaffected by either PO at luminal concentrations of 1, 10 or 50 μm, typical of intakes by Western and Asian populations as well as supplemental levels, respectively. The results of this model suggest that the proposed beneficial effects of supplemental levels of these PO compounds on bone mass in postmenopausal women more probably arise from direct effects on bone cells, and not by an indirect effect of these compounds on Ca absorption.

scholarly journals The mutual dependence between bone and gonads

2012 ◽  
Vol 213 (2) ◽  
pp. 107-114 ◽  
Author(s):  
Gerard Karsenty
Keyword(s):  
Bone Mass ◽  
Steroid Hormones ◽  
Male Fertility ◽  
Leydig Cells ◽  
Sex Steroid Hormones ◽  
Sex Steroid ◽  
Testable Hypothesis ◽  
Mass Energy ◽  
General Hypothesis ◽  
Bone Mass Accrual

It has long been known that sex steroid hormones regulate bone mass accrual. This observation raises the testable hypothesis that bone may in turn regulate the synthesis and secretion of sex steroid hormones in one or both genders. This hypothesis is comprised within a more general hypothesis that bone mass, energy metabolism, and reproduction are regulated coordinately. The identification of osteocalcin as an osteoblast-specific secreted molecule allows us to address this question in molecular terms. This review details how the regulation of male fertility by osteocalcin was unraveled, and how osteocalcin signaling in Leydig cells of the testis occurs. It also discusses the implication of this novel mode of regulation of testosterone synthesis observed in males but not in females.

scholarly journals Abnormal Thyroid Hormone Status Differentially Affects Bone Mass Accrual and Bone Strength in C3H/HeJ Mice: A Mouse Model of Type I Deiodinase Deficiency

2019 ◽  
Vol 10 ◽  
Author(s):  
Clarissa R. Zaitune ◽  
Tatiana L. Fonseca ◽  
Luciane P. Capelo ◽  
Fatima R. Freitas ◽  
Eduardo H. Beber ◽  
...  
Keyword(s):  
Thyroid Hormone ◽  
Mouse Model ◽  
Bone Mass ◽  
Bone Strength ◽  
Type I ◽  
Hormone Status ◽  
Bone Mass Accrual

scholarly journals Osteocyte Wnt/β-Catenin Signaling Is Required for Normal Bone Homeostasis

2010 ◽  
Vol 30 (12) ◽  
pp. 3071-3085 ◽  
Author(s):  
Ina Kramer ◽  
Christine Halleux ◽  
Hansjoerg Keller ◽  
Marco Pegurri ◽  
Jonathan H. Gooi ◽  
...  
Keyword(s):  
Bone Mass ◽  
Cortical Bone ◽  
Bone Cells ◽  
Osteoclast Differentiation ◽  
Axial Skeleton ◽  
Bone Homeostasis ◽  
Bone Thickness ◽  
Bone Mass Accrual ◽  
Canonical Wnt ◽  
Osteocyte Density

ABSTRACT β-Catenin-dependent canonical Wnt signaling plays an important role in bone metabolism by controlling differentiation of bone-forming osteoblasts and bone-resorbing osteoclasts. To investigate its function in osteocytes, the cell type constituting the majority of bone cells, we generated osteocyte-specific β-catenin-deficient mice (Ctnnb1 loxP/loxP ; Dmp1-Cre). Homozygous mutants were born at normal Mendelian frequency with no obvious morphological abnormalities or detectable differences in size or body weight, but bone mass accrual was strongly impaired due to early-onset, progressive bone loss in the appendicular and axial skeleton with mild growth retardation and premature lethality. Cancellous bone mass was almost completely absent, and cortical bone thickness was dramatically reduced. The low-bone-mass phenotype was associated with increased osteoclast number and activity, whereas osteoblast function and osteocyte density were normal. Cortical bone Wnt/β-catenin target gene expression was reduced, and of the known regulators of osteoclast differentiation, osteoprotegerin (OPG) expression was significantly downregulated in osteocyte bone fractions of mutant mice. Moreover, the OPG levels expressed by osteocytes were higher than or comparable to the levels expressed by osteoblasts during skeletal growth and at maturity, suggesting that the reduction in osteocytic OPG and the concomitant increase in osteocytic RANKL/OPG ratio contribute to the increased number of osteoclasts and resorption in osteocyte-specific β-catenin mutants. Together, these results reveal a crucial novel function for osteocyte β-catenin signaling in controlling bone homeostasis.

scholarly journals Renal Proximal Tubule Cell Cannabinoid-1 Receptor Regulates Bone Remodeling and Mass via a Kidney-to-Bone Axis

Cells ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 414
Author(s):  
Saja Baraghithy ◽  
Yael Soae ◽  
Dekel Assaf ◽  
Liad Hinden ◽  
Shiran Udi ◽  
...  
Keyword(s):  
Bone Mass ◽  
Proximal Tubule ◽  
Bone Remodeling ◽  
Kidney Function ◽  
Bone Cells ◽  
Critical Role ◽  
Renal Proximal Tubule ◽  
Proximal Tubule Cell ◽  
Protective Effects ◽  
Cannabinoid 1 Receptor

The renal proximal tubule cells (RPTCs), well-known for maintaining glucose and mineral homeostasis, play a critical role in the regulation of kidney function and bone remodeling. Deterioration in RPTC function may therefore lead to the development of diabetic kidney disease (DKD) and osteoporosis. Previously, we have shown that the cannabinoid-1 receptor (CB1R) modulates both kidney function as well as bone remodeling and mass via its direct role in RPTCs and bone cells, respectively. Here we employed genetic and pharmacological approaches that target CB1R, and found that its specific nullification in RPTCs preserves bone mass and remodeling both under normo- and hyper-glycemic conditions, and that its chronic blockade prevents the development of diabetes-induced bone loss. These protective effects of negatively targeting CB1R specifically in RPTCs were associated with its ability to modulate erythropoietin (EPO) synthesis, a hormone known to affect bone mass and remodeling. Our findings highlight a novel molecular mechanism by which CB1R in RPTCs remotely regulates skeletal homeostasis via a kidney-to-bone axis that involves EPO.

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