scholarly journals Sclerostin antibody treatment rescues the osteopenic bone phenotype of TGFβ inducible early gene‐1 knockout female mice

2020 ◽  
Vol 235 (7-8) ◽  
pp. 5679-5688 ◽  
Author(s):  
Anne Gingery ◽  
Malayannan Subramaniam ◽  
Kevin S. Pitel ◽  
Xiaodong Li ◽  
Hua Z. Ke ◽  
...  
Keyword(s):  
Early Gene ◽  
Antibody Treatment ◽  
Female Mice ◽  
Bone Phenotype ◽  
Osteopenic Bone ◽  
Sclerostin Antibody

scholarly journals Sclerostin Antibody Treatment Improves the Bone Phenotype ofCrtap-/-Mice, a Model of Recessive Osteogenesis Imperfecta

2016 ◽  
Vol 31 (5) ◽  
pp. 1030-1040 ◽  
Author(s):  
Ingo Grafe ◽  
Stefanie Alexander ◽  
Tao Yang ◽  
Caressa Lietman ◽  
Erica P Homan ◽  
...  
Keyword(s):  
Osteogenesis Imperfecta ◽  
Antibody Treatment ◽  
Bone Phenotype ◽  
Sclerostin Antibody

Osteogenesis imperfecta and short stature: effect of sclerostin antibody treatment in oim/oim mice

2013 ◽  
Author(s):  
Cardinal Mickael ◽  
Nyssen-Behets Catherine ◽  
Ominsky Mike ◽  
Devogelaer Jean-Pierre ◽  
H Manicourt Daniel
Keyword(s):  
Osteogenesis Imperfecta ◽  
Short Stature ◽  
Antibody Treatment ◽  
Sclerostin Antibody

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 Mutation of the Galectin-3 Glycan Binding Domain (Lgals3-R200S) Enhances Cortical Bone Expansion in Male and Trabecular Bone Mass in Female Mice

2020 ◽  
Author(s):  
Kevin A. Maupin ◽  
Daniel Dick ◽  
VARI Vivarium ◽  
Transgenics Core ◽  
Bart O. Williams
Keyword(s):  
Bone Mass ◽  
Trabecular Bone ◽  
Cortical Bone ◽  
Mutant Mice ◽  
Slight Variation ◽  
Female Mice ◽  
Bone Phenotype ◽  
Bone Expansion ◽  
Galectin 3 ◽  
Trabecular Bone Mass

AbstractThe study of galectin-3 is complicated by its ability to function both intracellularly and extracellularly. While the mechanism of galectin-3 secretion is unclear, studies have shown that the mutation of a highly conserved arginine to a serine in human galectin-3 (LGALS3-R186S) blocks glycan binding and secretion. To gain insight into the roles of extracellular and intracellular functions of galectin-3, we generated mice with the equivalent mutation (Lgals3-R200S) using CRISPR/Cas9-directed homologous recombination. Consistent with a reduction in galectin-3 secretion, we observed significantly reduced galectin-3 protein levels in the plasma of heterozygous and homozygous mutant mice. We observed a similar increased bone mass phenotype in Lgals3-R200S mutant mice at 36 weeks as we previously observed in Lgals3-KO mice with slight variation. Like Lgals3-KO mice, Lgals3-R200S females, but not males, had significantly increased trabecular bone mass. However, only male Lgals3-R200S mice showed increased cortical bone expansion, which we had previously observed in both male and female Lgals3-KO mice and only in female mice using a separate Lgals3 null allele (Lgals3). These results suggest that the trabecular bone phenotype of Lgals3-KO mice was driven primarily by loss of extracellular galectin-3. However, the cortical bone phenotype of Lgals3-KO mice may have also been influenced by loss of intracellular galectin-3. Future analyses of these mice will aid in identifying the cellular and molecular mechanisms that contribute to the Lgals3-deficient bone phenotype as well as aid in distinguishing the extracellular vs. intracellular roles of galectin-3 in various signaling pathways.

Sclerostin-Antibody Treatment Decreases Fracture Rates in Axial Skeleton and Improves the Skeletal Phenotype in Growing oim/oim Mice

2020 ◽  
Vol 106 (5) ◽  
pp. 494-508 ◽  
Author(s):  
Mickaël Cardinal ◽  
Alicia Dessain ◽  
Thomas Roels ◽  
Sébastien Lafont ◽  
Michael S. Ominsky ◽  
...  
Keyword(s):  
Axial Skeleton ◽  
Antibody Treatment ◽  
Skeletal Phenotype ◽  
Sclerostin Antibody

scholarly journals Time-dependent cellular and transcriptional changes in the osteoblast lineage associated with sclerostin antibody treatment in ovariectomized rats

Bone ◽  
2016 ◽  
Vol 84 ◽  
pp. 148-159 ◽  
Author(s):  
Scott Taylor ◽  
Michael S. Ominsky ◽  
Rong Hu ◽  
Efrain Pacheco ◽  
Yudong D. He ◽  
...  
Keyword(s):  
Time Dependent ◽  
Ovariectomized Rats ◽  
Antibody Treatment ◽  
Transcriptional Changes ◽  
Sclerostin Antibody ◽  
Osteoblast Lineage

scholarly journals 5-HT2A receptor loss does not alter acute fluoxetine-induced anxiety and exhibit sex-dependent regulation of cortical immediate early gene expression

2019 ◽  
Vol 3 (1) ◽  
Author(s):  
Minal Jaggar ◽  
Toshali Banerjee ◽  
Noelia Weisstaub ◽  
Jay A. Gingrich ◽  
Vidita A. Vaidya
Keyword(s):  
Immediate Early Gene ◽  
Brain Regions ◽  
Early Gene ◽  
Immediate Early ◽  
Neural Activation ◽  
Serum Corticosterone ◽  
Viral Oncogene ◽  
Female Mice ◽  
Murine Osteosarcoma ◽  
Viral Oncogene Homolog

Abstract Background: Acute treatment with the selective serotonin reuptake inhibitor (SSRI), fluoxetine (Flx), induces anxiety-like behavioral effects. The serotonin2A receptor (5-HT2A) is implicated in the modulation of anxiety-like behavior, however its contribution to the anxiogenic effects of acute Flx remains unclear. Here, we examined the role of the 5-HT2A receptor in the effects of acute Flx on anxiety-like behavior, serum corticosterone levels, neural activation and immediate early gene (IEG) expression in stress-responsive brain regions, using 5-HT2A receptor knockout (5-HT2A−/−) mice of both sexes. Methods: 5-HT2A−/− and wild-type (WT) male and female mice received a single administration of Flx or vehicle, and were examined for anxiety-like behavior, serum corticosterone levels, FBJ murine osteosarcoma viral oncogene homolog peptide (c-Fos) positive cell numbers in stress-responsive brain regions of the hypothalamus and prefrontal cortex (PFC), and PFC IEG expression. Results: The increased anxiety-like behavior and enhanced corticosterone levels evoked by acute Flx were unaltered in 5-HT2A−/− mice of both sexes. 5-HT2A−/− female mice exhibited a diminished neural activation in the hypothalamus in response to acute Flx. Further, 5-HT2A−/− male, but not female, mice displayed altered baseline expression of several IEGs (brain-derived neurotrophic factor (Bdnf), Egr2, Egr4, FBJ osteosarcoma gene (Fos), FBJ murine osteosarcoma viral oncogene homolog B (Fosb), Fos-like antigen 2 (Fosl2), Homer scaffolding protein (Homer) 1-3 (Homer1-3), Jun proto-oncogene (Jun)) in the PFC. Conclusion: Our results indicate that the increased anxiety and serum corticosterone levels evoked by acute Flx are not influenced by 5-HT2A receptor deficiency. However, the loss of function of the 5-HT2A receptor alters the degree of neural activation of the paraventricular nucleus (PVN) of the hypothalamus in response to acute Flx, and baseline expression of several IEGs in the PFC in a sexually dimorphic manner.

Effects of cocaine base paste on anxiety-like behavior and immediate-early gene expression in nucleus accumbens and medial prefrontal cortex of female mice

2019 ◽  
Vol 236 (12) ◽  
pp. 3525-3539 ◽  
Author(s):  
Bruno G. Berardino ◽  
Estefanía A. Fesser ◽  
Laura M. Belluscio ◽  
Octavio Gianatiempo ◽  
Nicolás Pregi ◽  
...  
Keyword(s):  
Gene Expression ◽  
Prefrontal Cortex ◽  
Nucleus Accumbens ◽  
Medial Prefrontal Cortex ◽  
Immediate Early Gene ◽  
Early Gene ◽  
Immediate Early ◽  
Early Gene Expression ◽  
Female Mice ◽  
Cocaine Base

scholarly journals Twist1 Inactivation in Dmp1-Expressing Cells Increases Bone Mass but Does Not Affect the Anabolic Response to Sclerostin Neutralization

2019 ◽  
Vol 20 (18) ◽  
pp. 4427 ◽  
Author(s):  
Karl J. Lewis ◽  
Roy B-J Choi ◽  
Emily Z. Pemberton ◽  
Whitney A. Bullock ◽  
Anthony B. Firulli ◽  
...  
Keyword(s):  
Bone Mass ◽  
Late Stage ◽  
Self Regulation ◽  
Biomechanical Properties ◽  
Loss Of Function ◽  
Antibody Treatment ◽  
Anabolic Response ◽  
Osteoblast Activity ◽  
Bone Properties ◽  
Sclerostin Antibody

Wnt signaling plays a major role in bone metabolism. Advances in our understanding of secreted regulators of Wnt have yielded several therapeutic targets to stimulate osteoanabolism—the most promising of which is the Wnt inhibitor sclerostin. Sclerostin antibody recently gained approval for clinical use to treat osteoporosis, but the biology surrounding sclerostin antagonism is still incompletely understood. Numerous factors regulate the efficacy of sclerostin inhibition on bone formation, a process known as self-regulation. In previous communications we reported that the basic helix-loop-helix transcription factor Twist1—a gene know to regulate skeletal development—is highly upregulated among the osteocyte cell population in mice treated with sclerostin antibody. In this communication, we tested the hypothesis that preventing Twist1 upregulation by deletion of Twist1 from late-stage osteoblasts and osteocytes would increase the efficacy of sclerostin antibody treatment, since Twist1 is known to restrain osteoblast activity in many models. Twist1-floxed loss-of-function mice were crossed to the Dmp1-Cre driver to delete Twist1 in Dmp1-expressing cells. Conditional Twist1 deletion was associated with a mild but significant increase in bone mass, as assessed by dual energy x-ray absorptiometry (DXA) and microCT (µCT) for many endpoints in both male and female mice. Biomechanical properties of the femur were not affected by conditional mutation of Twist1. Sclerostin antibody improved all bone properties significantly, regardless of Twist1 status, sex, or endpoint examined. No interactions were detected when Twist1 status and antibody treatment were examined together, suggesting that Twist1 upregulation in the osteocyte population is not an endogenous mechanism that restrains the osteoanabolic effect of sclerostin antibody treatment. In summary, Twist1 inhibition in the late-stage osteoblast/osteocyte increases bone mass but does not affect the anabolic response to sclerostin neutralization.

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