Faculty Opinions recommendation of Lrp5-independent activation of Wnt signaling by lithium chloride increases bone formation and bone mass in mice.

2006 ◽  
Author(s):  
Wim van Hul
Keyword(s):  
Bone Formation ◽  
Bone Mass ◽  
Wnt Signaling ◽  
Lithium Chloride

scholarly journals Lrp5-independent activation of Wnt signaling by lithium chloride increases bone formation and bone mass in mice

2005 ◽  
Vol 102 (48) ◽  
pp. 17406-17411 ◽  
Author(s):  
P. Clement-Lacroix ◽  
M. Ai ◽  
F. Morvan ◽  
S. Roman-Roman ◽  
B. Vayssiere ◽  
...  
Keyword(s):  
Bone Formation ◽  
Bone Mass ◽  
Wnt Signaling ◽  
Lithium Chloride

scholarly journals Lithium chloride enhances osteoblast differentiation and resists senile osteoporosis

2020 ◽  
Author(s):  
Yizhong Bao ◽  
Xiaoling Lv ◽  
Ying Tang ◽  
Xuanliang Ru ◽  
Jirong Wang ◽  
...  
Keyword(s):  
Bone Formation ◽  
Bone Mass ◽  
Wnt Signaling ◽  
Lithium Chloride ◽  
Osteoblast Differentiation ◽  
Marker Genes ◽  
Mineral Density ◽  
Alizarin Red ◽  
Trabecular Thickness ◽  
Senile Osteoporosis

Abstract Background Lithium chloride (LiCl) is commonly used in the clinic for the treatment of bipolar and other mental disorders. LiCl is an inhibitor of GSK-3β, and has been reported to modulate the balance of adipogenesis and osteogenesis. But, whether LiCl impacts bone formation and homeostasis in senile osteoporosis is still unclear. Methods Analysis of tibia in 2, 5, 7 and 10 months old C57BL/6 male mice were performed by MicroCT (μCT). 7 months old wild-type mice were treated with LiCl orally 0, 100 or 200 mg/kg for 3 months and then tested by μCT. The levels of osteogenesis marker genes and Wnt signaling target genes in bone marrow stromal cells (BMSCs) were detected by reverse transcription quantitative polymerase chain reaction and immunostaining. BMSCs were induced osteoblast differentiation and tested by Alizarin red S staining. Results μCT analyses of C57BL/6 mice showed that bone mineral density (BMD) and trabecular thickness (Tb.Th) increased until the bone mass peaked (5 months) and then began to fall subsequently. LiCl dramatically enhanced bone mass in the senile osteoporotic conditions, represented by increased ratio of bone volume to tissue volume (BV/TV), and decreased in trabeculae separation (Tb.Sp). Moreover, LiCl significantly increased both canonical osteoblastogenesis and Wnt signaling activity without affecting hormones. Conclusion This study uncovered the role of LiCl in canonical Wnt signaling and bone formation and have provided the evidence that LiCl may potentially repress senile osteoporosis.

scholarly journals R-spondin 3 deletion favors Erk phosphorylation to enhance Wnt signaling and bone formation

2021 ◽  
Author(s):  
Kenichi Nagano ◽  
Kei Yamana ◽  
Hiroaki Saito ◽  
Riku Kiviranta ◽  
Ana Clara Pedroni ◽  
...  
Keyword(s):  
Bone Density ◽  
Bone Formation ◽  
Bone Mass ◽  
Wnt Signaling ◽  
Erk Signaling ◽  
Canonical Wnt Signaling ◽  
Erk Phosphorylation ◽  
High Bone ◽  
Canonical Wnt

Abstract Activation of Wnt signaling leads to high bone density. The R-spondin family of four secreted glycoproteins (Rspo1-4) amplifies Wnt signaling. In humans, RSPO3 variants are strongly associated with bone density, but how RSPO3 affects skeletal homeostasis is not fully understood. Here we show that in mice Rspo3 haplo-insufficiency or its targeted deletion in osteoprogenitors lead to an increase in bone formation and bone mass. Contrary to expectations, Rspo3 haplo-insufficiency results in canonical Wnt signaling activation. Using mouse embryonic fibroblasts we show that Rspo3 deficiency leads to activation of Erk signaling, stabilizing β-catenin. Furthermore, Rspo3 haplo-insufficiency impairs Dkk1 efficacy in blocking canonical Wnt signaling and prevents the in vivo inhibition of bone formation and bone mass induced by osteoblast-targeted expression of Dkk1. We conclude that Rspo3 haplo-insufficiency/deficiency boosts canonical Wnt signaling by activating Erk signaling and impairing Dkk1’s inhibitory activity, which in turn lead to increased bone formation and bone mass.

scholarly journals R-spondin 3 deletion favors Erk phosphorylation to enhance Wnt signaling and bone formation

2021 ◽  
Author(s):  
Kenichi Nagano ◽  
Kei Yamana ◽  
Hiroaki Saito ◽  
Riku Kiviranta ◽  
Ana Clara Pedroni ◽  
...  
Keyword(s):  
Bone Density ◽  
Bone Formation ◽  
Bone Mass ◽  
Wnt Signaling ◽  
Erk Signaling ◽  
Canonical Wnt Signaling ◽  
Erk Phosphorylation ◽  
High Bone ◽  
Canonical Wnt

Abstract Activation of Wnt signaling leads to high bone density. The R-spondin family of four secreted glycoproteins (Rspo1-4) amplifies Wnt signaling. In humans, RSPO3 variants are strongly associated with bone density, but how RSPO3 affects skeletal homeostasis is not fully understood. Here we show that in mice Rspo3 haplo-insufficiency or its targeted deletion in osteoprogenitors lead to an increase in bone formation and bone mass. Contrary to expectations, Rspo3 haplo-insufficiency results in canonical Wnt signaling activation. Using mouse embryonic fibroblasts we show that Rspo3 deficiency leads to activation of Erk signaling, stabilizing β-catenin. Furthermore, Rspo3 haplo-insufficiency impairs Dkk1 efficacy in blocking canonical Wnt signaling and prevents the in vivo inhibition of bone formation and bone mass induced by osteoblast-targeted expression of Dkk1. We conclude that Rspo3 haplo-insufficiency/deficiency boosts canonical Wnt signaling by activating Erk signaling and impairing Dkk1’s inhibitory activity, which in turn lead to increased bone formation and bone mass.

scholarly journals Author Correction: Transferrin receptor 2 controls bone mass and pathological bone formation via BMP and Wnt signaling

2019 ◽  
Vol 1 (5) ◽  
pp. 584-584
Author(s):  
Martina Rauner ◽  
Ulrike Baschant ◽  
Antonella Roetto ◽  
Rosa Maria Pellegrino ◽  
Sandra Rother ◽  
...  
Keyword(s):  
Bone Formation ◽  
Bone Mass ◽  
Wnt Signaling ◽  
Transferrin Receptor ◽  
Transferrin Receptor 2

scholarly journals N-Cadherin Interacts with Axin and LRP5 To Negatively Regulate Wnt/β-Catenin Signaling, Osteoblast Function, and Bone Formation

2008 ◽  
Vol 29 (4) ◽  
pp. 953-964 ◽  
Author(s):  
Eric Haÿ ◽  
Emmanuel Laplantine ◽  
Valérie Geoffroy ◽  
Monique Frain ◽  
Thomas Kohler ◽  
...  
Keyword(s):  
Gene Expression ◽  
Bone Formation ◽  
Transgenic Mice ◽  
Bone Mass ◽  
Wnt Signaling ◽  
Adhesion Molecule ◽  
Molecular Complex ◽  
Tail Domain ◽  
Osteoblast Function ◽  
Canonical Wnt

ABSTRACT Wnt signaling plays an important role in the regulation of bone formation and bone mass. The mechanisms that regulate canonical Wnt signaling in osteoblasts are not fully understood. We show here a novel mechanism by which the adhesion molecule N-cadherin interacts with the Wnt coreceptor LRP5 and regulates canonical Wnt/β-catenin signaling in osteoblasts. We demonstrate that N-cadherin, besides associating with β-catenin at the membrane, forms a molecular complex with axin and LRP5 involving the LRP5 cytoplasmic tail domain. N-cadherin overexpression in osteoblasts increases N-cadherin-LRP5 interaction, causing increased β-catenin degradation and altered TCF/LEF transcription in response to Wnt3a. This mechanism results in decreased osteoblast gene expression and osteogenesis in basal conditions and in response to Wnt3a. Consistent with a functional mechanism, silencing N-cadherin expression in control cells increases TCF/LEF transcription and enhances the response to Wnt3a. Using N-cadherin transgenic mice, we show that increased N-cadherin-LRP5 interaction resulting from targeted overexpression of N-cadherin in osteoblasts causes increased β-catenin ubiquitination and results in cell-autonomous defective osteoblast function, reduced bone formation, and delayed bone mass acquisition. These data indicate that a previously unrecognized N-cadherin-axin-LRP5 interaction negatively regulates Wnt/β-catenin signaling and is critical in the regulation of osteoblast function, bone formation, and bone mass.

scholarly journals Sclerostin Antibody Treatment Increases Bone Formation, Bone Mass, and Bone Strength in a Rat Model of Postmenopausal Osteoporosis*

2009 ◽  
Vol 24 (4) ◽  
pp. 578-588 ◽  
Author(s):  
Xiaodong Li ◽  
Michael S Ominsky ◽  
Kelly S Warmington ◽  
Sean Morony ◽  
Jianhua Gong ◽  
...  
Keyword(s):  
Bone Formation ◽  
Bone Mass ◽  
Postmenopausal Osteoporosis ◽  
Bone Strength ◽  
Rat Model ◽  
Antibody Treatment ◽  
Sclerostin Antibody

scholarly journals The Development of Molecular Biology of Osteoporosis

2021 ◽  
Vol 22 (15) ◽  
pp. 8182
Author(s):  
Yongguang Gao ◽  
Suryaji Patil ◽  
Jingxian Jia
Keyword(s):  
Bone Resorption ◽  
Molecular Biology ◽  
Bone Formation ◽  
Bone Mass ◽  
Bone Remodeling ◽  
Bone Cells ◽  
Cell Activity ◽  
Bone Cell ◽  
Bone Disorders ◽  
Molecular Aspects

Osteoporosis is one of the major bone disorders that affects both women and men, and causes bone deterioration and bone strength. Bone remodeling maintains bone mass and mineral homeostasis through the balanced action of osteoblasts and osteoclasts, which are responsible for bone formation and bone resorption, respectively. The imbalance in bone remodeling is known to be the main cause of osteoporosis. The imbalance can be the result of the action of various molecules produced by one bone cell that acts on other bone cells and influence cell activity. The understanding of the effect of these molecules on bone can help identify new targets and therapeutics to prevent and treat bone disorders. In this article, we have focused on molecules that are produced by osteoblasts, osteocytes, and osteoclasts and their mechanism of action on these cells. We have also summarized the different pharmacological osteoporosis treatments that target different molecular aspects of these bone cells to minimize osteoporosis.

scholarly journals Ostm1 from Mouse to Human: Insights into Osteoclast Maturation

2020 ◽  
Vol 21 (16) ◽  
pp. 5600 ◽  
Author(s):  
Jean Vacher ◽  
Michael Bruccoleri ◽  
Monica Pata
Keyword(s):  
Bone Formation ◽  
Bone Mass ◽  
Bone Fractures ◽  
Bone Development ◽  
Bone Matrix ◽  
Adult Life ◽  
Cell Types ◽  
Severe Form ◽  
Isolation And Characterization

The maintenance of bone mass is a dynamic process that requires a strict balance between bone formation and resorption. Bone formation is controlled by osteoblasts, while osteoclasts are responsible for resorption of the bone matrix. The opposite functions of these cell types have to be tightly regulated not only during normal bone development, but also during adult life, to maintain serum calcium homeostasis and sustain bone integrity to prevent bone fractures. Disruption of the control of bone synthesis or resorption can lead to an over accumulation of bone tissue in osteopetrosis or conversely to a net depletion of the bone mass in osteoporosis. Moreover, high levels of bone resorption with focal bone formation can cause Paget’s disease. Here, we summarize the steps toward isolation and characterization of the osteopetrosis associated trans-membrane protein 1 (Ostm1) gene and protein, essential for proper osteoclast maturation, and responsible when mutated for the most severe form of osteopetrosis in mice and humans.

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