scholarly journals Cocaine and Amphetamine-Regulated Transcript May Regulate Bone Remodeling as a Circulating Molecule

Endocrinology ◽  
2008 ◽  
Vol 149 (8) ◽  
pp. 3933-3941 ◽  
Author(s):  
Manvendra K. Singh ◽  
Florent Elefteriou ◽  
Gerard Karsenty
Keyword(s):  
Bone Mass ◽  
Bone Remodeling ◽  
Third Ventricle ◽  
Fold Increase ◽  
Low Bone Mass ◽  
High Bone Mass ◽  
Peripheral Tissues ◽  
Osteoclast Number ◽  
High Bone ◽  
The Brain

Cocaine- and amphetamine-regulated transcript (CART) is one of the two known mediators of the leptin regulation of bone mass. Cart is expressed in both the brain and peripheral tissues such as the pituitary gland and the pancreatic islets. Cart−/− mice present a low bone mass phenotype due to an isolated increase in osteoclast number. In an effort to rescue their bone phenotype, we delivered recombinant CART in the third ventricle of the mutant mice but never recorded any improvement of the low bone mass, although this procedure could affect fat pad mass. In contrast, transgenic mice harboring a 2-fold increase in CART circulating level display a high bone mass due to an isolated decrease in osteoclast number and could rescue the low bone mass phenotype of the Cart−/− mice. Thus, our results suggest that in its capacity of a regulator of bone remodeling, CART may act more as a circulating molecule than a neuropeptide.

Exercise May Induce Reversible Low Bone Mass in Unloaded and High Bone Mass in Weight-Loaded Skeletal Regions

2001 ◽  
Vol 12 (11) ◽  
pp. 950-955 ◽  
Author(s):  
H. Magnusson ◽  
C. Lindén ◽  
C. Karlsson ◽  
K. J. Obrant ◽  
M. K. Karlsson
Keyword(s):  
Bone Mass ◽  
Low Bone Mass ◽  
High Bone Mass ◽  
High Bone

scholarly journals Cart Overexpression Is the Only Identifiable Cause of High Bone Mass in Melanocortin 4 Receptor Deficiency

Endocrinology ◽  
2006 ◽  
Vol 147 (7) ◽  
pp. 3196-3202 ◽  
Author(s):  
Jong Deok Ahn ◽  
Beatrice Dubern ◽  
Cecile Lubrano-Berthelier ◽  
Karine Clement ◽  
Gerard Karsenty
Keyword(s):  
Energy Metabolism ◽  
Bone Resorption ◽  
Bone Mass ◽  
Bone Remodeling ◽  
Neural Control ◽  
Osteoclast Differentiation ◽  
Serum Levels ◽  
High Bone Mass ◽  
Melanocortin 4 Receptor ◽  
High Bone

The neural regulation of bone remodeling has proven to be increasingly complex at the molecular level because it involves both positive and negative mediators of bone formation and resorption. One of the mediators expressed in hypothalamic neurons that leptin uses to inhibit osteoclast differentiation and thereby bone resorption is cocaine- and amphetamine-regulated transcript (CART). CART expression in the hypothalamus is increased in mice lacking melanocortin 4 receptor (Mc4r−/− mice). Moreover, we show here that humans or mice lacking only one allele of Mc4r display a decrease in bone resorption parameters, high bone mass, and an increase in CART serum levels and/or hypothalamic expression. To demonstrate that the Cart overexpression is the only identifiable cause for the high bone mass observed upon Mc4r inactivation, we removed one allele of Cart from mice either heterozygous or homozygous for Mc4r inactivation. This manipulation sufficed to either significantly improve or normalize bone resorption parameters, without improving the energy metabolism disturbance that characterizes Mc4r-deficient mice. These results identify CART signaling as the main if not only molecular pathway accounting for the decrease in bone resorption leading to high bone mass in mice and humans deficient in Mc4r. As importantly, they also indicate that CART regulates bone resorption independently of the role it may exert in energy metabolism, suggesting that the neural control of appetite and bone remodeling are independent of each other.

scholarly journals In Vivo Analysis of Wnt Signaling in Bone

Endocrinology ◽  
2007 ◽  
Vol 148 (6) ◽  
pp. 2630-2634 ◽  
Author(s):  
Donald A. Glass ◽  
Gerard Karsenty
Keyword(s):  
Bone Mass ◽  
Wnt Signaling ◽  
Bone Remodeling ◽  
Signaling Pathway ◽  
Mouse Models ◽  
Osteoclast Differentiation ◽  
Wnt Signaling Pathway ◽  
Human Beings ◽  
High Bone Mass ◽  
High Bone

Bone remodeling requires osteoblasts and osteoclasts working in concert to maintain a constant bone mass. The dysregulation of signaling pathways that affect osteoblast or osteoclast differentiation or function leads to either osteopenia or high bone mass. The discovery that activating and inactivating mutations in low-density lipoprotein receptor-related protein 5, a putative Wnt coreceptor, led to high bone mass and low bone mass in human beings, respectively, generated a tremendous amount of interest in the possible role of the Wnt signaling pathway in the regulation of bone remodeling. A number of mouse models have been generated to study a collection of Wnt signaling molecules that have been identified as regulators of bone mass. These mouse models help establish the canonical Wnt signaling pathway as a major regulator of chondrogenesis, osteoblastogenesis, and osteoclastogenesis. This review will summarize these advances.

scholarly journals Amylin inhibits bone resorption while the calcitonin receptor controls bone formation in vivo

2004 ◽  
Vol 164 (4) ◽  
pp. 509-514 ◽  
Author(s):  
Romain Dacquin ◽  
Rachel A. Davey ◽  
Catherine Laplace ◽  
Régis Levasseur ◽  
Howard A. Morris ◽  
...  
Keyword(s):  
Bone Resorption ◽  
Bone Formation ◽  
Bone Mass ◽  
Dependent Manner ◽  
Calcitonin Receptor ◽  
Low Bone Mass ◽  
High Bone Mass ◽  
High Bone

Amylin is a member of the calcitonin family of hormones cosecreted with insulin by pancreatic β cells. Cell culture assays suggest that amylin could affect bone formation and bone resorption, this latter function after its binding to the calcitonin receptor (CALCR). Here we show that Amylin inactivation leads to a low bone mass due to an increase in bone resorption, whereas bone formation is unaffected. In vitro, amylin inhibits fusion of mononucleated osteoclast precursors into multinucleated osteoclasts in an ERK1/2-dependent manner. Although Amylin +/− mice like Amylin-deficient mice display a low bone mass phenotype and increased bone resorption, Calcr +/− mice display a high bone mass due to an increase in bone formation. Moreover, compound heterozygote mice for Calcr and Amylin inactivation displayed bone abnormalities observed in both Calcr +/− and Amylin +/− mice, thereby ruling out that amylin uses CALCR to inhibit osteoclastogenesis in vivo. Thus, amylin is a physiological regulator of bone resorption that acts through an unidentified receptor.

scholarly journals Mice Lacking Cathepsin K Maintain Bone Remodeling but Develop Bone Fragility Despite High Bone Mass

2006 ◽  
Vol 21 (6) ◽  
pp. 865-875 ◽  
Author(s):  
Chao Yang Li ◽  
Karl J Jepsen ◽  
Robert J Majeska ◽  
Jian Zhang ◽  
Rujing Ni ◽  
...  
Keyword(s):  
Bone Mass ◽  
Bone Remodeling ◽  
Cathepsin K ◽  
Bone Fragility ◽  
High Bone Mass ◽  
High Bone

Intrauterine stress induces bone loss in adult offspring of C3H/HeJ mice having high bone mass phenotype but not C57BL/6J mice with low bone mass phenotype

Bone ◽  
2016 ◽  
Vol 87 ◽  
pp. 114-119 ◽  
Author(s):  
M. Raygorodskaya ◽  
Y. Gabet ◽  
C. Shochat ◽  
E. Kobyliansky ◽  
A. Torchinsky ◽  
...  
Keyword(s):  
Bone Loss ◽  
Bone Mass ◽  
Adult Offspring ◽  
Low Bone Mass ◽  
High Bone Mass ◽  
High Bone ◽  
High Bone Mass Phenotype

scholarly journals Mice lacking DKK1 in T cells exhibit high bone mass and are protected from estrogen deficiency-induced bone loss

iScience ◽  
2021 ◽  
pp. 102224
Author(s):  
Juliane Lehmann ◽  
Sylvia Thiele ◽  
Ulrike Baschant ◽  
Tilman D. Rachner ◽  
Christof Niehrs ◽  
...  
Keyword(s):  
T Cells ◽  
Bone Loss ◽  
Bone Mass ◽  
Estrogen Deficiency ◽  
High Bone Mass ◽  
High Bone
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