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

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

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

Time-dependent effects of oestradiol and progesterone on hypothalamic catecholamine turnover in ovariectomized rats

1985 ◽  
Vol 106 (3) ◽  
pp. 303-309 ◽  
Author(s):  
C. Hiemke ◽  
D. Bruder ◽  
M. C. Michel ◽  
R. Ghraf
Keyword(s):  
Turnover Rate ◽  
Brain Area ◽  
Serum Levels ◽  
Time Dependent ◽  
Ovariectomized Rats ◽  
Dopamine Turnover ◽  
Turnover Rates ◽  
Noradrenaline Turnover ◽  
Time Element ◽  
Increased Sensitivity

ABSTRACT Long-term ovariectomized rats received a single injection of 20 μg oestradiol benzoate (OB) which reduced the serum levels of LH for at least 3 days. The inhibitory effects were accompanied by time-dependent alterations of noradrenaline and dopamine turnover rates in the mediobasal hypothalamus (MBH) and the preoptic-anterior hypothalamic brain area (POAH). Oestradiol markedly interfered with the time-dependent variations of noradrenaline and dopamine turnover seen in the MBH of untreated ovariectomized animals during daylight hours. In the POAH the turnover rate of noradrenaline decreased 2 days after priming with OB and then increased in the afternoon of day 3. The increase of noradrenaline turnover in the POAH was accompanied by a low afternoon turnover rate of dopamine in the M BH and by an increased sensitivity of the LH secretory system to progesterone. Dopamine and noradrenaline turnover involve a time element. While the negative feedback actions of oestradiol do not seem to be associated with changes in dopamine or noradrenaline turnover, the results support the view that the induction of LH afternoon surges depends upon an increase of stimulatory noradrenergic inputs to the POAH and a decrease of inhibitory dopaminergic inputs in the MBH. J. Endocr. (1985) 106, 303–309

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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