Both NPY‐Expressing and CART‐Expressing Neurons Increase Energy Expenditure and Trabecular Bone Mass in Response to AP1 Antagonism, But Have Opposite Effects on Bone Resorption

2020 ◽  
Vol 35 (6) ◽  
pp. 1107-1118
Author(s):  
Anna Idelevich ◽  
Kazusa Sato ◽  
Byron Avihai ◽  
Kenichi Nagano ◽  
Antonin Galien ◽  
...  
Keyword(s):  
Bone Resorption ◽  
Energy Expenditure ◽  
Bone Mass ◽  
Trabecular Bone ◽  
Increase Energy Expenditure ◽  
Trabecular Bone Mass

scholarly journals Targeted Inactivation of Rin3 Increases Trabecular Bone Mass by Reducing Bone Resorption and Favouring Bone Formation

2021 ◽  
Author(s):  
Mahéva Vallet ◽  
Antonia Sophocleous ◽  
Anna E. Törnqvist ◽  
Asim Azfer ◽  
Rob van’t Hof ◽  
...  
Keyword(s):  
Bone Resorption ◽  
Bone Formation ◽  
Bone Mass ◽  
Trabecular Bone ◽  
Wild Type ◽  
Common Genetic Variants ◽  
Trabecular Bone Mass ◽  
Skeletal Phenotype ◽  
Targeted Inactivation ◽  
Do So

AbstractCommon genetic variants at the RIN3 locus on chromosome 14q32 predispose to Paget’s disease of bone (PDB) but the mechanisms by which they do so are unknown. Here, we analysed the skeletal phenotype of female mice with targeted inactivation of the mouse Rin3 gene (Rin3−/−) as compared with wild-type littermates. The Rin3−/− mice had higher trabecular bone volume (BV/TV%) compared with wild type. Mean ± standard deviation values at the distal femur at 8 weeks were 9.0 ± 2.5 vs. 7.0 ± 1.5 (p = 0.002) and at 52 weeks were 15.8 ± 9.5 vs. 8.5 ± 4.2 (p = 0.002). No differences were observed in femoral cortical bone parameters with the exception of marrow diameter which was significantly smaller in 52-week-old Rin3−/− mice compared to wild type: (0.43 mm ± 0.1 vs. 0.57 mm ± 0.2 (p = 0.001). Bone histomorphometry showed a lower osteoclast surface / bone surface (Oc.S/BS%) at 8 weeks in Rin3−/− mice compared to wild type (24.1 ± 4.7 vs. 29.7 ± 6.6; p = 0.025) but there were no significant differences in markers of bone formation at this time. At 52 weeks, Oc.S/BS did not differ between genotypes but single labelled perimeter (SL.Pm/B.Pm (%)) was significantly higher in Rin3−/− mice (24.4 ± 6.4 vs. 16.5 ± 3.8, p = 0.003). We conclude that Rin3 negatively regulates trabecular bone mass in mice by inhibiting osteoclastic bone resorption and favouring bone formation. Our observations also suggest that the variants that predispose to PDB in humans probably do so by causing a gain-in-function of RIN3.

scholarly journals Correction to: Targeted Inactivation of Rin3 Increases Trabecular Bone Mass by Reducing Bone Resorption and Favouring Bone Formation

2021 ◽  
Author(s):  
Mahéva Vallet ◽  
Antonia Sophocleous ◽  
Anna E. Törnqvist ◽  
Asim Azfer ◽  
Rob van’t Hof ◽  
...  
Keyword(s):  
Bone Resorption ◽  
Bone Formation ◽  
Bone Mass ◽  
Trabecular Bone ◽  
Trabecular Bone Mass ◽  
Targeted Inactivation

A correction to this paper has been published: https://doi.org/10.1007/s00223-021-00849-w

Quantitative computed tomography in measurement of vertebral trabecular bone mass

1988 ◽  
Vol 29 (6) ◽  
pp. 719-725 ◽  
Author(s):  
M. Nilsson ◽  
O. Johnell ◽  
K. Jonsson ◽  
I. Redlund-Johnell
Keyword(s):  
Computed Tomography ◽  
Bone Mass ◽  
Trabecular Bone ◽  
Quantitative Computed Tomography ◽  
Vertebral Trabecular Bone ◽  
Trabecular Bone Mass

scholarly journals Chronic administration of Glucagon-like peptide-1 receptor agonists improves trabecular bone mass and architecture in ovariectomised mice

Bone ◽  
2015 ◽  
Vol 81 ◽  
pp. 459-467 ◽  
Author(s):  
M. Pereira ◽  
J. Jeyabalan ◽  
C.S. Jørgensen ◽  
M. Hopkinson ◽  
A. Al-Jazzar ◽  
...  
Keyword(s):  
Bone Mass ◽  
Trabecular Bone ◽  
Chronic Administration ◽  
Receptor Agonists ◽  
Trabecular Bone Mass ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

scholarly journals Disruption of the p53 Gene Results in Preserved Trabecular Bone Mass and Bone Formation After Mechanical Unloading

2002 ◽  
Vol 17 (1) ◽  
pp. 119-127 ◽  
Author(s):  
Akinori Sakai ◽  
Takeshi Sakata ◽  
Shinya Tanaka ◽  
Ryuji Okazaki ◽  
Naoki Kunugita ◽  
...  
Keyword(s):  
Bone Formation ◽  
Bone Mass ◽  
Trabecular Bone ◽  
P53 Gene ◽  
Mechanical Unloading ◽  
Trabecular Bone Mass

scholarly journals Prolyl Hydroxylase Domain-Containing Protein 3 Gene Expression in Chondrocytes Is Not Essential for Bone Development in Mice

Cells ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 2200
Author(s):  
Weirong Xing ◽  
Sheila Pourteymoor ◽  
Gustavo A. Gomez ◽  
Yian Chen ◽  
Subburaman Mohan
Keyword(s):  
Gene Expression ◽  
Bone Formation ◽  
Bone Mass ◽  
Trabecular Bone ◽  
Bone Volume ◽  
Endochondral Bone Formation ◽  
Chondrocyte Differentiation ◽  
Trabecular Bone Volume ◽  
Endochondral Bone ◽  
Trabecular Bone Mass

We previously showed that conditional disruption of the Phd2 gene in chondrocytes led to a massive increase in long bone trabecular bone mass. Loss of Phd2 gene expression or inhibition of PHD2 activity by a specific inhibitor resulted in a several-fold compensatory increase in Phd3 expression in chondrocytes. To determine if expression of PHD3 plays a role in endochondral bone formation, we conditionally disrupted the Phd3 gene in chondrocytes by crossing Phd3 floxed (Phd3flox/flox) mice with Col2α1-Cre mice. Loss of Phd3 expression in the chondrocytes of Cre+; Phd3flox/flox conditional knockout (cKO) mice was confirmed by real time PCR. At 16 weeks of age, neither body weight nor body length was significantly different in the Phd3 cKO mice compared to Cre−; Phd3flox/flox wild-type (WT) mice. Areal BMD measurements of total body as well as femur, tibia, and lumbar skeletal sites were not significantly different between the cKO and WT mice at 16 weeks of age. Micro-CT measurements revealed significant gender differences in the trabecular bone volume adjusted for tissue volume at the secondary spongiosa of the femur and the tibia for both genotypes, but no genotype difference was found for any of the trabecular bone measurements of either the femur or the tibia. Trabecular bone volume of distal femur epiphysis was not different between cKO and WT mice. Histology analyses revealed Phd3 cKO mice exhibited a comparable chondrocyte differentiation and proliferation, as evidenced by no changes in cartilage thickness and area in the cKO mice as compared to WT littermates. Consistent with the in vivo data, lentiviral shRNA-mediated knockdown of Phd3 expression in chondrocytes did not affect the expression of markers of chondrocyte differentiation (Col2, Col10, Acan, Sox9). Our study found that Phd2 but not Phd3 expressed in chondrocytes regulates endochondral bone formation, and the compensatory increase in Phd3 expression in the chondrocytes of Phd2 cKO mice is not the cause for increased trabecular bone mass in Phd2 cKO mice.

scholarly journals Myeloid Lineage Ablation of Phlpp1 Regulates M-CSF Signaling and Tempers Bone Resorption in Female Mice

2021 ◽  
Vol 22 (18) ◽  
pp. 9702
Author(s):  
Ismael Y. Karkache ◽  
Jeyaram R. Damodaran ◽  
David H. H. Molstad ◽  
Kim C. Mansky ◽  
Elizabeth W. Bradley
Keyword(s):  
Bone Resorption ◽  
Bone Mass ◽  
Cell Types ◽  
Serum Markers ◽  
In Vitro Assays ◽  
Bovine Bone ◽  
Micro Computed Tomography ◽  
Myeloid Lineage ◽  
Trabecular Bone Mass

Prior work demonstrated that Phlpp1 deficiency alters trabecular bone mass and enhances M-CSF responsiveness, but the cell types and requirement of Phlpp1 for this effect were unclear. To understand the function of Phlpp1 within myeloid lineage cells, we crossed Phlpp1 floxed mice with mice harboring LysM-Cre. Micro-computed tomography of the distal femur of 12-week-old mice revealed a 30% increase in bone volume per total volume of Phlpp1 female conditional knockouts, but we did not observe significant changes within male Phlpp1 cKOLysM mice. Bone histomorphmetry of the proximal tibia further revealed that Phlpp1 cKOLysM females exhibited elevated osteoclast numbers, but conversely had reduced levels of serum markers of bone resorption as compared to littermate controls. Osteoblast number and serum markers of bone formation were unchanged. In vitro assays confirmed that Phlpp1 ablation enhanced osteoclast number and area, but limited bone resorption. Additionally, reconstitution with exogenous Phlpp1 suppressed osteoclast numbers. Dose response assays demonstrated that Phlpp1−/− cells are more responsive to M-CSF, but reconstitution with Phlpp1 abrogated this effect. Furthermore, small molecule-mediated Phlpp inhibition enhanced osteoclast numbers and size. Enhanced phosphorylation of Phlpp substrates—including Akt, ERK1/2, and PKCζ—accompanied these observations. In contrast, actin cytoskeleton disruption occurred within Phlpp inhibitor treated osteoclasts. Moreover, Phlpp inhibition reduced resorption of cells cultured on bovine bone slices in vitro. Our results demonstrate that Phlpp1 deficiency within myeloid lineage cells enhances bone mass by limiting bone resorption while leaving osteoclast numbers intact; moreover, we show that Phlpp1 represses osteoclastogenesis and controls responses to M-CSF.

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