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

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.

journal_name

Endocrinology

journal_title

Endocrinology

authors

Millard SM,Wang L,Wattanachanya L,O'Carroll D,Fields AJ,Pang J,Kazakia G,Lotz JC,Nissenson RA

doi

10.1210/en.2016-1365

subject

Has Abstract

pub_date

2017-06-01 00:00:00

pages

1715-1726

issue

6

eissn

0013-7227

issn

1945-7170

pii

3605333

journal_volume

158

pub_type

杂志文章
  • Cholesterogenic lanosterol 14alpha-demethylase (CYP51) is an immediate early response gene.

    abstract::Lanosterol 14alpha-demethylase (CYP51) responds to cholesterol feedback regulation through sterol regulatory element binding proteins (SREBPs). The proximal promoter of CYP51 contains a conserved region with clustered regulatory elements: GC box, cAMP-response elements (CRE-like), and sterol regulatory element (SRE). ...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/en.2005-0781

    authors: Fink M,Acimovic J,Rezen T,Tansek N,Rozman D

    更新日期:2005-12-01 00:00:00

  • Ultrastructural localization of relaxin immunoreactivity in corpora lutea of pregnant rats.

    abstract::Relaxin was localized in cells of corpora lutea of pregnant rats at the ultrastructural level using a highly specific antirat relaxin serum and the unlabeled peroxidase-antiperoxidase technique. Electron-dense, membrane-bound granules (maximum diameter, 270 nm), which are present in luteal cells during the last third ...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/endo-114-4-1124

    authors: Anderson MB,Sherwood OD

    更新日期:1984-04-01 00:00:00

  • Characterization of the calf uterine androgen receptor and its activation to the deoxyribonucleic acid-binding state.

    abstract::The androgen receptor (AR) from calf uterine cytosol has been studied in terms of steroid-binding affinity, hormone dissociation kinetics, and DNA-cellulose-binding capacity. The binding affinity for three androgens, analyzed under conditions where binding to progesterone receptor did not occur, decreased in the order...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/endo-118-2-851

    authors: de Boer W,Lindh M,Bolt J,Brinkmann A,Mulder E

    更新日期:1986-02-01 00:00:00

  • Insulin-like growth factor-1 (IGF-1) in mice reduces weight loss during starvation.

    abstract::Plasma concentrations of IGF-1 decrease markedly during starvation secondary to a reduction in somatotropic receptors in the liver. We investigated whether IGF-1 administration during starvation in mice inhibits the catabolic state normally observed. Plasma concentrations of IGF-1 in starved mice receiving IGF-1 thera...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/endo-125-5-2793

    authors: O'Sullivan U,Gluckman PD,Breier BH,Woodall S,Siddiqui RA,McCutcheon SN

    更新日期:1989-11-01 00:00:00

  • Control of rat preadipocyte adipose conversion by ovarian status: regional specificity and possible involvement of the mitogen-activated protein kinase-dependent and c-fos signaling pathways.

    abstract::As ovariectomy induces obesity in rats, we have investigated the influence of ovariectomy and hormone replacement on the proliferation and differentiation capacities of rat cultured preadipocytes removed from different fat depots (femoral sc, parametrial, and perirenal). Ovariectomy induced increased proliferation and...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/endo.138.7.5246

    authors: Lacasa D,Garcia E,Agli B,Giudicelli Y

    更新日期:1997-07-01 00:00:00

  • Regeneration of Functional Adrenal Tissue Following Bilateral Adrenalectomy.

    abstract::It is assumed that after complete bilateral adrenalectomy (ADX), no adrenal tissue will redevelop and adrenal hormone levels will remain low and unaffected by stress. However, anecdotal observations in animals and in patients suggest that under some unknown circumstances the opposite can occur. Herein, we studied whet...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/en.2017-00505

    authors: Gotlieb N,Albaz E,Shaashua L,Sorski L,Matzner P,Rosenne E,Amram B,Benbenishty A,Golomb E,Ben-Eliyahu S

    更新日期:2018-01-01 00:00:00

  • Identification of the chicken growth hormone-releasing hormone receptor (GHRH-R) mRNA and gene: regulation of anterior pituitary GHRH-R mRNA levels by homologous and heterologous hormones.

    abstract::GHRH stimulates GH secretion in chickens as in mammals. However, nothing is known about the chicken GHRH receptor (GHRH-R). Here we report the cDNA sequence of chicken GHRH-R. Comparison of the cDNA sequence with the chicken genome localized the GHRH-R gene to chicken chromosome 2 and indicated that the chicken GHRH-R...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/en.2005-1534

    authors: Porter TE,Ellestad LE,Fay A,Stewart JL,Bossis I

    更新日期:2006-05-01 00:00:00

  • A central domain binding site in insulin-like growth factor binding protein-5 for the acid-labile subunit.

    abstract::Like insulin-like growth factor binding protein-3 (IGFBP-3), IGFBP-5 forms a ternary complex with insulin-like growth factor (IGF)-I or IGF-II, and the acid-labile subunit (ALS). The study of IGFBP-5/IGFBP-6 chimeric proteins with amino-terminal and middle domain swaps, has revealed the existence of a site in the midd...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/endo.141.1.7375

    authors: Twigg SM,Kiefer MC,Zapf J,Baxter RC

    更新日期:2000-01-01 00:00:00

  • Suppression of iodide uptake and thyroid hormone synthesis with stimulation of the type I interferon system by double-stranded ribonucleic acid in cultured human thyroid follicles.

    abstract::Although viral infection is thought to be associated with subacute thyroiditis and probably with autoimmune thyroid disease, possible changes in thyroid function during the prodromal period of infection or subclinical infection remain largely unknown. Recently, it was shown that pathogen-associated molecular patterns ...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/en.2006-1638

    authors: Yamazaki K,Suzuki K,Yamada E,Yamada T,Takeshita F,Matsumoto M,Mitsuhashi T,Obara T,Takano K,Sato K

    更新日期:2007-07-01 00:00:00

  • Insulin and norepinephrine regulate ghrelin secretion from a rat primary stomach cell culture.

    abstract::Ghrelin is a peptide hormone primarily produced in the previously unidentified X/A endocrine cells of the stomach. Extensive studies have focused on the effects of ghrelin on growth hormone release and appetite regulation. However, the mechanisms regulating ghrelin secretion are less understood. In the present study, ...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/en.2012-1040

    authors: Gagnon J,Anini Y

    更新日期:2012-08-01 00:00:00

  • Identification and characterization of binding proteins for inhibin and activin in human serum and follicular fluids.

    abstract::Inhibins and activins are produced by a variety of tissues and may have important endocrine and paracrine roles in development, reproduction, and hematopoiesis. However, little is known regarding the physical properties or concentrations of inhibin and activin in biological fluids. Binding proteins for inhibin or acti...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/endo.132.1.7678220

    authors: Krummen LA,Woodruff TK,DeGuzman G,Cox ET,Baly DL,Mann E,Garg S,Wong WL,Cossum P,Mather JP

    更新日期:1993-01-01 00:00:00

  • Histaminergic activation of the hypothalamic-pituitary-adrenal axis.

    abstract::Centrally administered histamine (HA) stimulates the secretion of adenohypophysial POMC-derived peptides, which subsequently cause release of corticosterone. The effect of HA on POMC-derived peptide release is indirect, and it is possible that hypothalamic neurons containing corticotropin-releasing hormone (CRH), argi...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/endo.135.3.8070360

    authors: Kjaer A,Larsen PJ,Knigge U,Warberg J

    更新日期:1994-09-01 00:00:00

  • Reovirus induction of MHC class II antigen in rat thyroid cells.

    abstract::We have previously demonstrated that cultured rat thyroid cells do not exhibit constitutive expression of major histocompatibility (MHC) class II antigens. Using reovirus types 1 and 3, we infected 1B-6 cells (a cloned derivative of the Fisher rat cell line FRTL-5), and found a dose-dependent induction of thyroid cell...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/endo-124-1-543

    authors: Neufeld DS,Platzer M,Davies TF

    更新日期:1989-01-01 00:00:00

  • In situ photolinked nuclear progesterone receptors of human breast cancer cells: subunit molecular weights after transformation and translocation.

    abstract::The subunit structure of mammalian cytoplasmic progesterone receptors (PR) has been difficult to study because these proteins are subject to in vitro proteolysis; the structure of nuclear PR is unknown. We have now developed an in situ photoaffinity labeling method for PR that permits study of their subunits with mini...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/endo-113-6-2195

    authors: Horwitz KB,Alexander PS

    更新日期:1983-12-01 00:00:00

  • Inhibition of transcription affects synthesis of steroidogenic acute regulatory protein and steroidogenesis in MA-10 mouse Leydig tumor cells.

    abstract::Hormonal induction of steroidogenesis in the adrenal and gonads is dependent on the synthesis and function of the steroidogenic acute regulatory protein (StAR). As a first approach to investigate the role of translation in the control of StAR expression, we examined StAR protein synthesis and steroid production in MA-...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/endo.138.11.5535

    authors: Clark BJ,Combs R,Hales KH,Hales DB,Stocco DM

    更新日期:1997-11-01 00:00:00

  • In vivo characterization of high Basal signaling from the ghrelin receptor.

    abstract::The receptor for the orexigenic peptide, ghrelin, is one of the most constitutively active 7TM receptors known, as demonstrated under in vitro conditions. Change in expression of a constitutively active receptor is associated with change in signaling independent of the endogenous ligand. In the following study, we fou...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/en.2008-1638

    authors: Petersen PS,Woldbye DP,Madsen AN,Egerod KL,Jin C,Lang M,Rasmussen M,Beck-Sickinger AG,Holst B

    更新日期:2009-11-01 00:00:00

  • Effects of somatostatin and urotensin II on tilapia pituitary prolactin release and interactions between somatostatin, osmotic pressure Ca++, and adenosine 3',5'-monophosphate in prolactin release in vitro.

    abstract::Both somatostatin (SRIF) and urotensin II, a dodecapeptide from the teleost caudal neurosecretory system, inhibit PRL release from the organ-cultured rostral pars distalis of the tilapia, Sarotherodon mossambicus, in a dose-related manner. The inhibitory action of SRIF on PRL release was completely prevented by the pr...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/endo-110-3-910

    authors: Grau EG,Nishioka RS,Bern HA

    更新日期:1982-03-01 00:00:00

  • Selenium-dependent pre- and posttranscriptional mechanisms are responsible for sexual dimorphic expression of selenoproteins in murine tissues.

    abstract::Important enzymes for thyroid hormone metabolism, antioxidative defense, and intracellular redox control contain selenocysteine (Sec) in their active centers. Expression of these selenoproteins is tightly controlled, and a sex-specific phenotype is observed on disturbance of selenium (Se) transport in mice. Therefore,...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/en.2006-0689

    authors: Riese C,Michaelis M,Mentrup B,Götz F,Köhrle J,Schweizer U,Schomburg L

    更新日期:2006-12-01 00:00:00

  • Extracellular superoxide dismutase functions as a major repressor of hypoxia-induced erythropoietin gene expression.

    abstract::Hypoxia and biological responses to hypoxia are commonly encountered in both normal and pathologic cellular processes. Here we report that extracellular superoxide dismutase (EC-SOD) plays a major role in regulating the magnitude of hypoxia-induced erythropoietin (Epo) gene expression, thus implicating superoxide as a...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/en.2004-1007

    authors: Zelko IN,Folz RJ

    更新日期:2005-01-01 00:00:00

  • Adrenalectomy-induced alterations of calmodulin-dependent hippocampal adenylate cyclase activity: role of guanine nucleotide-binding proteins.

    abstract::Ca2+/calmodulin-dependent processes are altered by manipulations of the hypothalamic-pituitary-adrenal axis. In particular, adrenalectomy (ADX) attenuates hippocampal, but not cortical, calmodulin-dependent adenylate cyclase activity measured during the active (waking) phase of rats. The involvement of calmodulin- and...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/endo.134.2.8299580

    authors: Gannon MN,Akompong T,Billingsley ML,McEwen BS

    更新日期:1994-02-01 00:00:00

  • Further studies on the hypercalcemic effect of acute calcitonin deficiency in rats.

    abstract::Studies were carried out to determine the origin of the immediate increase in plasma calcium following acute calcitonin deficiency in mature rats. Animals were pre-labelled with 45calcium 24 hours and 4 weeks before thyroparathyroidectomy (TPTX) and 1 hour, 24 hours, 2 and 4 weeks before nephrectomy and TPTX and bled ...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/endo-98-2-534

    authors: Kalu DN,Hadji-Georgopoulos A,Foster GV

    更新日期:1976-02-01 00:00:00

  • Basal and growth hormone-induced hepatic messenger ribonucleic acid expression of insulin-like growth factor-I (IGF-I) and IGF-binding protein-3 is independent of hyperinsulinemia and increased energy status in the genetically obese Zucker rat.

    abstract::Genetically obese Zucker rats, like obese humans, have normal or elevated circulating insulin-like growth factor-I (IGF-I) levels in the presence of low GH secretion. Hyperinsulinemia, increased energy status, or other nutritional factors associated with obesity could be responsible for these findings directly by incr...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/endo.138.3.4975

    authors: Melián E,Velasco B,Barrios R,Sanchez-Franco F

    更新日期:1997-03-01 00:00:00

  • Restitution of blood volume after hemorrhage: inhibition by somatostatin.

    abstract::To determine whether glucagon plays a significant role in the restitution of blood volume after hemorrhage, pentobarbital-anesthetized dogs were treated with somatostatin (SRIF). The administration of SRIF (14 micrograms/kg.h) prevented the increase in osmolality and the complete restitution of plasma protein and bloo...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/endo-110-6-1945

    authors: Byrnes GJ,Engeland WC,Gann DS

    更新日期:1982-06-01 00:00:00

  • Localization of renal 11 beta-dehydrogenase by in situ hybridization: autocrine not paracrine protector of the mineralocorticoid receptor.

    abstract::In the kidney, 11 beta-dehydrogenase (11 beta-DH) converts the active steroid cortisol to inactive cortisone (corticosterone to 11-dehydrocorticosterone in the rat). In man, congenital and acquired deficiency of 11 beta-dehydrogenase are rare causes of hypertension in which cortisol acts as a potent mineralocorticoid....

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/endo-128-4-2129

    authors: Stewart PM,Whorwood CB,Barber P,Gregory J,Monder C,Franklyn JA,Sheppard MC

    更新日期:1991-04-01 00:00:00

  • Developmental regulation of unique adenosine 3',5'-monophosphate-specific phosphodiesterase variants during rat spermatogenesis.

    abstract::Previous studies from our laboratory have shown that messenger RNAs (mRNAs) coding for a cAMP-specific phosphodiesterase (PDE4A) are present in mature rat and mouse germ cells. However, no information is available about the properties of the expressed proteins. To determine their structure and regulation, the PDE4A is...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/endo.137.6.8641200

    authors: Naro F,Zhang R,Conti M

    更新日期:1996-06-01 00:00:00

  • Facilitative glucose transporter type 1 is differentially regulated by progesterone and estrogen in murine and human endometrial stromal cells.

    abstract::Embryo implantation is a highly synchronized event between an activated blastocyst and a receptive endometrium. The success of this process relies on the dynamic interplay of estrogen (E(2)) and progesterone (P(4)), however, the details of this interaction are not entirely clear. Recent data implicate E(2) and P(4) in...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/en.2008-1081

    authors: Frolova A,Flessner L,Chi M,Kim ST,Foyouzi-Yousefi N,Moley KH

    更新日期:2009-03-01 00:00:00

  • Endothelin-1 promotes steroidogenesis and stimulates protooncogene expression in transformed murine Leydig cells.

    abstract::The effects of endothelin-1 (ET-1), a potent vasoconstrictor and mitogen to various cell types, on proliferation and differentiated functions of the murine Leydig tumor cell line MA-10 were investigated. Kinetic binding experiments at room temperature showed that [125I] ET-1 bound to MA-10 cells and reached equilibriu...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/endo.132.2.8425480

    authors: Ergul A,Glassberg MK,Majercik MH,Puett D

    更新日期:1993-02-01 00:00:00

  • Leptin inhibits angiotensin II-induced intracellular calcium increase and vasoconstriction in the rat aorta.

    abstract::Besides its role in body weight control leptin may also act as a vasoactive hormone. This study was designed to investigate whether leptin modifies angiotensin II (ANG II)-induced vascular responses. The expression of functional leptin receptors (OB-Rb) was detected in vascular smooth muscle cells (VSMCs) from adult W...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/en.2002-220075

    authors: Fortuño A,Rodríguez A,Gómez-Ambrosi J,Muñiz P,Salvador J,Díez J,Frühbeck G

    更新日期:2002-09-01 00:00:00

  • Expression and development of a functional plasmalemmal 5-hydroxytryptamine transporter by thyroid follicular cells.

    abstract::5-Hydroxytryptamine (5-HT) is synthesized and secreted by thyroid parafollicular (PF) cells. As all PF granules contain 5-HT, it is released whenever PF cells secrete. Because 5-HT stimulates follicular (F) cells and can modulate their response to TSH, 5-HT has been proposed to be a paracrine PF to F cell transmitter....

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/endo.137.10.8828510

    authors: Tamir H,Hsiung SC,Liu KP,Blakely RD,Russo AF,Clark MS,Nunez EA,Gershon MD

    更新日期:1996-10-01 00:00:00

  • Testosterone-responsive mouse kidney glycosphingolipids: developmental and inbred strain effects.

    abstract::Mouse kidney and urinary glycosphingolipids from developing C57BL/6J and adults of several other inbred strains were analyzed by high performance liquid chromatographic techniques. Glycosphingolipids from male and female C57BL/6J kidneys were similar until the fifth week of age. Galactosylceramide containing nonhydrox...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/endo-113-1-251

    authors: McCluer RH,Deutsch CK,Gross SK

    更新日期:1983-07-01 00:00:00