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.

PRECLINICAL STUDIES OF ALENDRONATE

1999 ◽  
Vol 03 (03) ◽  
pp. 209-216
Author(s):  
Jenny Zhao ◽  
Yebin Jiang ◽  
Harry K. Genant
Keyword(s):  
Bone Resorption ◽  
Bone Loss ◽  
Bone Formation ◽  
Bone Turnover ◽  
Trabecular Bone ◽  
Bending Strength ◽  
Bone Volume ◽  
Prostaglandin E ◽  
Dependent Manner ◽  
Dose Dependent

Alendronate has been developed for the treatment of diseases characterized by increased bone resorption, such as osteoporosis. It increases metaphyseal bone density, bone volume, femoral bending strength and vertebral compressive strength, in a dose-dependent manner, in growing, intact rats. In ovariectomized (OVX) rats, alendronate increases femoral bone mass and tibial trabecular bone volume in a dose-dependent manner, and increases femoral midshaft bending strength. In rats immobilized by unilateral sciatic neurectomy, it inhibits bone loss and is dose-dependent. In rats, alendronate prevents high-turnover osteopenia induced by hyperthyroidism or by administration of immunosuppressant agent cyclosporin-A. Also in rats, treatment with prostaglandin E 2 and alendronate does not inhibit prostaglandin E 2-induced stimulation of bone formation on endocortical and periosteal surfaces. It does, however, prevent prostaglandin E 2-induced cortical bone porosity as a result of increased bone resorption, leading to an increase in cortical thickness and an increase in three-point bending strength of the femoral midshaft. At up to five times the dose used for treatment of osteoporosis in clinical trials, alendronate causes no abnormalities in bone remodeling, bone structure, or structural mechanical properties of the femur or vertebrae in intact beagles. Treatment with alendronate before or during fracture healing, or both, has no adverse effects on the union, strength, bone formation or mineralization of bone in mature beagle dogs. In intact minipigs, sodium fluoride increases and alendronate decreases bone turnover, while sodium fluoride, but not alendronate, decreases L4 strength and femoral stiffness. Small-angle X-ray scattering and backscattered electron imaging show that the trabecular bone matrix is more uniformly mineralized after alendronate treatment. In OVX baboons, which show bone changes similar to those seen in postmenopausal women, alendronate prevents an increase in bone turnover, and increases both bone volume and strength in vertebrae, in a dose-dependent manner. Alendronate also reduces the bone loss of alveolar support associated with periodontitis in monkeys. Thus, alendronate inhibits bone resorption and bone turnover, increases bone quantity accompanied by improved bone quality in some of the intact animals and in the animal models.

scholarly journals The Dual Role of Vitamin K2 in “Bone-Vascular Crosstalk”: Opposite Effects on Bone Loss and Vascular Calcification

Nutrients ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 1222
Author(s):  
Domitilla Mandatori ◽  
Letizia Pelusi ◽  
Valeria Schiavone ◽  
Caterina Pipino ◽  
Natalia Di Pietro ◽  
...  
Keyword(s):  
Bone Loss ◽  
Vascular Calcification ◽  
Vascular System ◽  
The Elderly ◽  
Food Supplement ◽  
Vitamin K2 ◽  
Bioactive Molecules ◽  
Calcium Deposition ◽  
Age Related

Osteoporosis (OP) and vascular calcification (VC) represent relevant health problems that frequently coexist in the elderly population. Traditionally, they have been considered independent processes, and mainly age-related. However, an increasing number of studies have reported their possible direct correlation, commonly defined as “bone-vascular crosstalk”. Vitamin K2 (VitK2), a family of several natural isoforms also known as menaquinones (MK), has recently received particular attention for its role in maintaining calcium homeostasis. In particular, VitK2 deficiency seems to be responsible of the so-called “calcium paradox” phenomenon, characterized by low calcium deposition in the bone and its accumulation in the vessel wall. Since these events may have important clinical consequences, and the role of VitK2 in bone-vascular crosstalk has only partially been explained, this review focuses on its effects on the bone and vascular system by providing a more recent literature update. Overall, the findings reported here propose the VitK2 family as natural bioactive molecules that could be able to play an important role in the prevention of bone loss and vascular calcification, thus encouraging further in-depth studies to achieve its use as a dietary food supplement.

Age-related bone loss in CW-1 female mice: An in vivo model for postmenopausal osteoporosis

Bone ◽  
1986 ◽  
Vol 7 (5) ◽  
pp. 395
Author(s):  
B. Bar-Shira ◽  
R. Coleman ◽  
A. Reznick ◽  
E. Steinhagen-Thiessen ◽  
M. Silbermann
Keyword(s):  
Bone Loss ◽  
Postmenopausal Osteoporosis ◽  
In Vivo Model ◽  
Female Mice ◽  
Age Related

Bone Formation and Resorption as the Determinants of Trabecular Bone Volume in Normal and Osteoporotic Men

1984 ◽  
Vol 29 (3) ◽  
pp. 171-175 ◽  
Author(s):  
B. E. C. Nordin ◽  
J. Aaron ◽  
R. Speed ◽  
R. M. Francis ◽  
N. Makins
Keyword(s):  
Bone Formation ◽  
Trabecular Bone ◽  
Inverse Function ◽  
Positive Function ◽  
Bone Volume ◽  
Trabecular Bone Volume ◽  
Age Related ◽  
Osteoporosis In Men ◽  
Spinal Osteoporosis ◽  
The Mean

Trabecular bone volume, forming surface and percent surface resorption have been determined in iliac crest samples obtained post mortem from 43 young men and 49 elderly men and in biopsies obtained from 22 males with spinal osteoporosis. The mean bone volume was significantly lower in the old than in the young controls and significantly lower again in the osteoporotic cases. Forming surfaces were significantly lower in the old than the young controls but were not different as between old controls and cases of osteoporosis. Percent surface resorption was the same in young and old controls but significantly increased in the osteoporotics. Multiple regression analysis showed that trabecular bone volume was a significant positive function of forming surface and a significant inverse function of fractional surface resorption. Age-related (simple) osteoporosis in men appears to be due to reduced bone formation whereas pathological (accelerated) osteoporosis is due to increased bone resorption.

The type 2 cannabinoid receptor protects against age-related bone loss and ovariectomy induced bone loss by stimulating bone formation

Bone ◽  
2010 ◽  
Vol 47 ◽  
pp. S42-S43
Author(s):  
A. Sophocleous⁎ ◽  
E. Landao-Bassonga ◽  
R. van 't Hof ◽  
S.H. Ralston ◽  
A.I. Idris
Keyword(s):  
Bone Loss ◽  
Bone Formation ◽  
Cannabinoid Receptor ◽  
Age Related

scholarly journals Modeling the Mechanical Consequences of Age-Related Trabecular Bone Loss by XFEM Simulation

2016 ◽  
Vol 2016 ◽  
pp. 1-12 ◽  
Author(s):  
Ruoxun Fan ◽  
He Gong ◽  
Xianbin Zhang ◽  
Jun Liu ◽  
Zhengbin Jia ◽  
...  
Keyword(s):  
Mechanical Properties ◽  
Bone Loss ◽  
Trabecular Bone ◽  
Bone Age ◽  
The Elderly ◽  
Extended Finite Element ◽  
Age Related ◽  
Trabecular Bone Loss ◽  
Complete Failure ◽  
Fracture Processes

The elderly are more likely to suffer from fracture because of age-related trabecular bone loss. Different bone loss locations and patterns have different effects on bone mechanical properties. Extended finite element method (XFEM) can simulate fracture process and was suited to investigate the effects of bone loss on trabecular bone. Age-related bone loss is indicated by trabecular thinning and loss and may occur at low-strain locations or other random sites. Accordingly, several ideal normal and aged trabecular bone models were created based on different bone loss locations and patterns; then, fracture processes from crack initiation to complete failure of these models were observed by XFEM; finally, the effects of different locations and patterns on trabecular bone were compared. Results indicated that bone loss occurring at low-strain locations was more detrimental to trabecular bone than that occurring at other random sites; meanwhile, the decrease in bone strength caused by trabecular loss was higher than that caused by trabecular thinning, and the effects of vertical trabecular loss on mechanical properties were more severe than horizontal trabecular loss. This study provided a numerical method to simulate trabecular bone fracture and distinguished different effects of the possible occurrence of bone loss locations and patterns on trabecular bone.

scholarly journals Factores de diferenciación génica y su futuro en el tratamiento de la osteoporosis: de la adipogénesis a la osteoblastogénesis, ¿del mismo modo y en sentido contrario?

2018 ◽  
Vol 5 (4) ◽  
pp. 21-25
Author(s):  
Pedro Sánchez Márquez ◽  
Carlos Arturo Révérend Lizcano
Keyword(s):  
Transcription Factor ◽  
Bone Loss ◽  
Bone Formation ◽  
Endochondral Ossification ◽  
Related Factors ◽  
Senile Osteoporosis ◽  
Age Related ◽  
Post Traumatic

El presente artículo tiene como objetivo presentar de forma resumida los diferentes factores que están involucrados en la diferenciación y el mantenimiento del fenotipo óseo, en contraste con los factores adipogénicos, cuya expresión determina procesos de diferenciación mutuamente excluyentes. Por otro lado, se propone el posible uso terapéutico para distintas patologías óseas como la osteoporosis. Los datos fueron obtenidos de estudios clínicos aleatorizados y de revisión, en idioma español e inglés, de los últimos 15 años, que incluyeran los términos Mesh: Osteoporosis; Osteoporoses; Osteoporosis, Post-Traumatic; Osteoporosis, Senile; Osteoporosis, Age-Related; Bone Loss, Age-Related; Factors, Transcription; Transcription Factor; Adipogeneses; Bone Formation; Osteoclastogenesis; Endochondral Ossification; Endochondral Ossifications; Ossification, Endochondral; Ossification, Physiological; Ossification, Physiologic.

scholarly journals Reduced bone formation in males and increased bone resorption in females drive bone loss in hemophilia A mice

2019 ◽  
Vol 3 (3) ◽  
pp. 288-300 ◽  
Author(s):  
M. Neale Weitzmann ◽  
Susanne Roser-Page ◽  
Tatyana Vikulina ◽  
Daiana Weiss ◽  
Li Hao ◽  
...  
Keyword(s):  
Bone Resorption ◽  
Bone Loss ◽  
Bone Formation ◽  
Hemophilia A ◽  
Genetic Disorder ◽  
Clotting Factor ◽  
Female Mice ◽  
Peak Mass ◽  
Traditional Risk Factors ◽  
Traumatic Hemorrhage

Abstract Hemophilia A (HA), a rare X-linked recessive genetic disorder caused by insufficient blood clotting factor VIII, leaves affected individuals susceptible to spontaneous and traumatic hemorrhage. Although males generally exhibit severe symptoms, due to variable X inactivation, females can also be severely impacted. Osteoporosis is a disease of the skeleton predisposing patients to fragility fracture, a cause of significant morbidity and mortality and a common comorbidity in HA. Because the causes of osteoporosis in HA are unclear and in humans confounded by other traditional risk factors for bone loss, in this study, we phenotyped the skeletons of F8 total knockout (F8TKO) mice, an animal model of severe HA. We found that trabecular bone accretion in the axial and appendicular skeletons of male F8TKO mice lagged significantly between 2 and 6 months of age, with more modest cortical bone decline. By contrast, in female mice, diminished bone accretion was mostly limited to the cortical compartment. Interestingly, bone loss was associated with a decline in bone formation in male mice but increased bone resorption in female mice, a possible result of sex steroid insufficiency. In conclusion, our studies reveal a sexual dimorphism in the mechanism driving bone loss in male and female F8TKO mice, preventing attainment of peak bone mass and strength. If validated in humans, therapies aimed at promoting bone formation in males but suppressing bone resorption in females may be indicated to facilitate attainment of peak mass in children with HA to reduce the risk for fracture later in life.

Abstract 220: Transcriptional Analysis Of Caveolin And Cavin In The Male And Female Ageing Mouse Heart Following Ischemic Stress

2014 ◽  
Vol 115 (suppl_1) ◽  
Author(s):  
Can J Kiessling ◽  
Melissa Reichelt ◽  
John Headrick ◽  
Kevin Ashton
Keyword(s):  
G Protein ◽  
Ischemic Tolerance ◽  
Transcriptional Analysis ◽  
Membrane Microdomains ◽  
G Protein Coupled Receptor ◽  
Male And Female ◽  
Female Mice ◽  
Age Related ◽  
G Protein Coupled ◽  
Ischemic Stress

Cardioprotection against infarction and dysfunction in the myocardium involves G-protein-coupled receptor signalling orchestrated by specialised membrane microdomains termed caveolae. The caveolin protein family consist of three subtypes: caveolin-1, −2 and −3 (Cav1-3) and are responsible for the formation of caveolae and hypothesized to orchestrate cardioprotective signalling. Caveolin-3 deficiency and overexpression has been shown to attenuate and restore cardioprotection, respectively. Recently, a family of four related proteins known as cavins (Cavin1-4) have been implicated as regulators of caveolae formation and function. The roles and expression distribution of the cavin family is currently unknown in cardiac tissue. In this study hearts were isolated from 8, 16, 32 and 48 week male and female mice and subjected to normoxic perfusion (80 min) or ischemic stress (20 min global ischemia, 60 min reperfusion). RT-qPCR was used to assess differential gene expression of caveolin and cavin subtypes across these ages in both sexes. Decreased post-ischemic pressure development and increased LDH release were observed in 32 and 48 week old relative to 8 week old male hearts hearts, indicative of age-related loss of ischemic tolerance. Females showed greater tolerance to ischemia at 32 and 48 week old hearts when compared to male counterparts. In normoxic male 48 week old hearts, Cav1,-2,-3 and Cavin1 were significantly repressed, whilst post-ischemic male 48 week old hearts demonstrated significant repression of Cav3 and Cavin1 only. Normoxic female hearts showed no significant changes in caveolin and cavin transcript expression over the aging time course. However, post-ischemic female 48 week old hearts showing significant down-regulation of Cav3 only. Taken together, alterations in caveolin and cavin expression may contribute to the age-related loss of ischemic tolerance and G-protein-coupled receptor-mediated protection in aging male and female mice hearts.

5 alpha-Dihydrotestosterone partially restores cancellous bone volume in osteopenic ovariectomized rats

1994 ◽  
Vol 267 (6) ◽  
pp. E853-E859 ◽  
Author(s):  
J. H. Tobias ◽  
A. Gallagher ◽  
T. J. Chambers
Keyword(s):  
Bone Resorption ◽  
Bone Loss ◽  
Bone Formation ◽  
Cancellous Bone ◽  
Bone Growth ◽  
Bone Volume ◽  
Ovariectomized Rats ◽  
Trabecular Thickness ◽  
Longitudinal Bone Growth ◽  
Periosteal Bone Formation

Although androgens are thought to be important for skeletal maintenance in females and males, little is known about the mechanisms involved. To investigate this question further, we examined the effects of administering 0.01, 0.1, or 1.0 mg/kg 5 alpha-dihydrotestosterone (DHT) for 60 days on the skeleton of ovariectomized rats. Treatment was delayed until 90 days after ovariectomy to enable bone loss to stabilize. We found that ovariectomy markedly reduced cancellous bone volume of the proximal tibial metaphysis due to a combination of loss and thinning of trabeculae. Cancellous bone volume was partially restored by all doses of DHT, with trabecular thickness, but not number, returning to that of sham-operated animals. DHT also stimulated longitudinal bone growth and endosteal and periosteal bone formation and suppressed histomorphometric indexes of cancellous bone resorption. This suggests that DHT influences skeletal metabolism in osteopenic ovariectomized rats both by stimulating bone formation and suppressing resorption, although it is unclear which, if any, of these actions predominate at cancellous sites.

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