NFATC2-knock-out mice reveal a high bone mass phenotype

Bone ◽  
2010 ◽  
Vol 47 ◽  
pp. S40
Author(s):  
M. Rauner⁎ ◽  
W. Bauer ◽  
I. Habermann ◽  
M. Haase ◽  
C. Goettsch ◽  
...  
Keyword(s):  
Bone Mass ◽  
High Bone Mass ◽  
Knock Out ◽  
High Bone ◽  
High Bone Mass Phenotype ◽  
Knock Out Mice

scholarly journals Selective deletion of the receptor for CSF1, c-fms, in osteoclasts results in a high bone mass phenotype, smaller osteoclasts in vivo and an impaired response to an anabolic PTH regimen

PLoS ONE ◽  
2021 ◽  
Vol 16 (2) ◽  
pp. e0247199
Author(s):  
Meiling Zhu ◽  
Ben-hua Sun ◽  
Erin Nevius ◽  
Jared Kaplan ◽  
João Pereira ◽  
...  
Keyword(s):  
Bone Mass ◽  
Trabecular Bone ◽  
Cathepsin K ◽  
Normal Weight ◽  
High Bone Mass ◽  
Knock Out ◽  
High Bone ◽  
Knock Out Mice

The receptor for Colony Stimulating Factor 1 (CSF1), c-fms, is highly expressed on mature osteoclasts suggesting a role for this cytokine in regulating the function of these cells. Consistent with this idea, in vitro studies have documented a variety of effects of CSF1 in mature osteoclasts. To better define the role of CSF1 in these cells, we conditionally deleted c-fms in osteoclasts (c-fms-OC-/-) by crossing c-fmsflox/flox mice with mice expressing Cre under the control of the cathepsin K promoter. The c-fms-OC-/- mice were of normal weight and had normal tooth eruption. However, when quantified by DXA, bone mass was significantly higher in the spine and femur of female knock out mice and in the femurs of male knock out mice. MicroCT analyses of femurs showed that female c-fms-OC-/- mice had significantly increased trabecular bone mass with a similar trend in males and both sexes demonstrated significantly increased trabecular number and reduced trabecular spacing. Histomorphometric analysis of the femoral trabecular bone compartment demonstrated a trend towards increased numbers of osteoclasts, +26% in Noc/BPm and +22% in OcS/BS in the k/o animals but this change was not significant. However, when the cellular volume of osteoclasts was quantified, the c-fms-OC-/- cells were found to be significantly smaller than controls. Mature osteoclasts show a marked spreading response when exposed to CSF1 in a non-gradient fashion. However, osteoclasts freshly isolated from c-fms-OC-/- mice had a near complete abrogation of this response. C-fms-OC-/- mice treated with (1–34)hPTH 80 ng/kg/d in single daily subcutaneous doses for 29 days showed an attenuated anabolic response in trabecular bone compared to wild-type animals. Taken together, these data indicate an important non-redundant role for c-fms in regulating mature osteoclast function in vivo.

A genomic and transcriptomic approach to the high bone mass phenotype: evidences of heterogeneity and of additive effects of TWIST1, IL6R, DLX3, and PPARG

2013 ◽  
Author(s):  
Patricia Sarrion ◽  
Leonardo Mellibovsky ◽  
Roser Urreizti ◽  
Sergi Civit ◽  
Neus Cols ◽  
...  
Keyword(s):  
Bone Mass ◽  
Additive Effects ◽  
High Bone Mass ◽  
High Bone ◽  
High Bone Mass Phenotype

scholarly journals Sex dimorphic regulation of osteoprogenitor progesterone in bone stromal cells

2017 ◽  
Vol 59 (4) ◽  
pp. 351-363 ◽  
Author(s):  
Alexander Kot ◽  
Zhendong A Zhong ◽  
Hongliang Zhang ◽  
Yu-An Evan Lay ◽  
Nancy E Lane ◽  
...  
Keyword(s):  
Mouse Model ◽  
Bone Mass ◽  
Gene Transcription ◽  
Conditional Knockout ◽  
Sequencing Analysis ◽  
Wild Type ◽  
High Bone Mass ◽  
Matrix Interaction ◽  
High Bone ◽  
High Bone Mass Phenotype

Increasing peak bone mass is a promising strategy to prevent osteoporosis. A mouse model of global progesterone receptor (PR) ablation showed increased bone mass through a sex-dependent mechanism. Cre-Lox recombination was used to generate a mouse model of osteoprogenitor-specific PR inactivation, which recapitulated the high bone mass phenotype seen in the PR global knockout mouse mode. In this work, we employed RNA sequencing analysis to evaluate sex-independent and sex-dependent differences in gene transcription of osteoprogenitors of wild-type and PR conditional knockout mice. PR deletion caused marked sex hormone-dependent changes in gene transcription in male mice as compared to wild-type controls. These transcriptional differences revealed dysregulation in pathways involving immunomodulation, osteoclasts, bone anabolism, extracellular matrix interaction and matrix interaction. These results identified many potential mechanisms that may explain our observed high bone mass phenotype with sex differences when PR was selectively deleted in the MSCs.

Interrelationship between Metabolic and High Bone Mass Phenotype in a Mouse Model of Adult-Onset, Isolated, GH-Deficiency (AOiGHD).

2010 ◽  
pp. P1-219-P1-219
Author(s):  
JW Bracey ◽  
RA Skinner ◽  
NS Akel ◽  
AB Reddy ◽  
J Cordoba-Chacon ◽  
...  
Keyword(s):  
Mouse Model ◽  
Bone Mass ◽  
Gh Deficiency ◽  
Adult Onset ◽  
High Bone Mass ◽  
High Bone ◽  
High Bone Mass Phenotype

scholarly journals Novel LRP5 Missense Mutation in a Patient With a High Bone Mass Phenotype Results in Decreased DKK1-Mediated Inhibition of Wnt Signaling*

2007 ◽  
Vol 22 (5) ◽  
pp. 708-716 ◽  
Author(s):  
Wendy Balemans ◽  
Jean-Pierre Devogelaer ◽  
Erna Cleiren ◽  
Elke Piters ◽  
Emanuelle Caussin ◽  
...  
Keyword(s):  
Bone Mass ◽  
Wnt Signaling ◽  
Missense Mutation ◽  
High Bone Mass ◽  
High Bone ◽  
High Bone Mass Phenotype

scholarly journals F-Spondin Deficient Mice Have a High Bone Mass Phenotype

PLoS ONE ◽  
2014 ◽  
Vol 9 (5) ◽  
pp. e98388 ◽  
Author(s):  
Glyn D. Palmer ◽  
Mukundan G. Attur ◽  
Qing Yang ◽  
James Liu ◽  
Paxton Moon ◽  
...  
Keyword(s):  
Bone Mass ◽  
High Bone Mass ◽  
High Bone ◽  
High Bone Mass Phenotype ◽  
Deficient Mice

scholarly journals Role of CaMKK2 in Osteocytes within the Bone Microenvironment

2018 ◽  
Vol 1 (1) ◽  
Author(s):  
Nick Clough ◽  
Justin Williams ◽  
Uma Sankar
Keyword(s):  
Bone Mass ◽  
Bone Cell ◽  
T Antigen ◽  
Dendritic Morphology ◽  
Bone Biology ◽  
High Bone Mass ◽  
High Bone ◽  
High Bone Mass Phenotype ◽  
Outstanding Question

Background and Hypothesis:   The Ca+2/calmodulin (CaM)-mediated protein kinase kinase 2 (CaMKK2) is a multi-functional kinase with effects on cell proliferation, differentiation and metabolism. The role of CaMKK2 in bone has been explored with its ablation favoring osteoblasts to osteoclasts and bone mass accrual as observed in Camkk2-/- mice, or following its inhibition by STO-609. One outstanding question is whether the anabolic effects of CaMKK2 are bone-cell intrinsic. While analyzing mice harboring bone-cell specific deletion of CaMKK2, we observed a high bone mass phenotype when the kinase is deleted from osteocytes, the most abundant cells within the bone. We therefore hypothesized that the loss of CaMKK2 enhances osteocyte differentiation.  Experimental Design or Project Methods:  We used two osteocyte cell lines MLO-Y4 and MLO-A5, both generated from mice expressing the immortalizing T-antigen, to test our hypothesis. The MLO-A5 line has post-osteoblast/pre-osteocyte characteristics while the MLO-Y4 line has mature osteocyte characteristics. CaMKK2 expression was silenced in MLO-A5 cells using Lentiviruses encoding CaMKK2 short hairpin (sh) RNA constructs. STO-609 was employed to inhibit CaMKK2 in the MLO-Y4 line as it proved resistant to transfection. Immunoblotting was used to verify CaMKK2 silencing/inhibition. Comparisons on cell morphologies were observed using immunofluorescence. As osteocytes are defined by dendritic morphology, the number of dendritic processes were analyzed. Additionally, the differences in the expression of the osteocyte markers SOST, E11 and DMP1 were examined by qRT-PCR.  Results:  To be finalized.  Conclusion and Potential Impact:  Overall, our studies will provide more information towards understanding the role of CaMKK2 in bone biology and aid its development as a therapeutic target in the treatment of osteoporosis.

Cnot7-Null Mice Exhibit High Bone Mass Phenotype and Modulation of BMP Actions

2007 ◽  
Vol 22 (8) ◽  
pp. 1217-1223 ◽  
Author(s):  
Kaoru Washio-Oikawa ◽  
Takahisa Nakamura ◽  
Michihiko Usui ◽  
Mitsuhiro Yoneda ◽  
Youichi Ezura ◽  
...  
Keyword(s):  
Bone Mass ◽  
High Bone Mass ◽  
High Bone ◽  
High Bone Mass Phenotype
Sign in / Sign up

Export Citation Format

Share Document