Summary of Study ST001704
This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR001090. The data can be accessed directly via it's Project DOI: 10.21228/M8T12F This work is supported by NIH grant, U2C- DK119886.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
This study contains a large results data set and is not available in the mwTab file. It is only available for download via FTP as data file(s) here.
Study ID | ST001704 |
Study Title | Sclerostin antibody increases trabecular bone and bone mechanical properties by increasing osteoblast activity damaged by whole-body irradiation in mice |
Study Type | Basic research |
Study Summary | Irradiation therapy causes bone deterioration and increased risk for skeletal-related events. Irradiation interferes with trabecular architecture through increased osteoclastic activity, decreased osteoblastic activity, and increased adipocyte expansion in the bone marrow (BM), which further compounds bone-related disease. Neutralizing antibodies to sclerostin (Scl-Ab) increase bone mass and strength by increasing bone formation and reducing bone resorption. We hypothesized that treatment with Scl-Ab would attenuate the adverse effects of irradiation by increasing bone volume and decreasing BM adipose tissue (BMAT), resulting in better quality bone. In this study, 12-week-old female C57BL/6J mice were exposed to 6 Gy whole-body irradiation or were non-irradiated, then administered Scl-Ab (25 mg/kg) or vehicle weekly for 5 weeks. Femoral µCT analysis confirmed that the overall effect of IR significantly decreased trabecular bone volume/total volume (Tb.BV/TV) (2-way ANOVA, p<0.0001) with a -43.8% loss in Tb.BV/TV in the IR control group. Scl-Ab independently increased Tb.BV/TV by 3.07-fold in non-irradiated and 3.6-fold in irradiated mice (2-way ANOVA, p<0.0001). Irradiation did not affect cortical parameters, although Scl-Ab increased cortical thickness and area significantly in both irradiated and non-irradiated mice (2-way ANOVA, p<0.0001). Femoral mechanical testing confirmed Scl-Ab significantly increased bending rigidity and ultimate moment independently of irradiation (2-way ANOVA, p<0.0001). Static and dynamic histomorphometry of the femoral metaphysis revealed osteoblast vigor, not number, was significantly increased in the irradiated mice treated with Scl-Ab. Systemic alterations were assessed through serum lipidomic analysis, which showed that Scl-Ab normalized lipid profiles in the irradiated group. This data supports the theory of sclerostin as a novel contributor to the regulation of osteoblast activity after irradiation. Overall, our data support the hypothesis that Scl-Ab ameliorates the deleterious effects of whole-body irradiation on bone and adipose tissue in a mouse model. Our findings suggest that future research into localized and systemic therapies after irradiation exposure is warranted. |
Institute | Mainehealth |
Last Name | Vary |
First Name | Calvin |
Address | 81 Research Drive, Scarborough, ME, USA 04074 |
varyc@mmc.org | |
Phone | 2073968148 |
Submit Date | 2021-02-10 |
Raw Data Available | Yes |
Raw Data File Type(s) | wiff |
Analysis Type Detail | MS(Dir. Inf.) |
Release Date | 2021-03-01 |
Release Version | 1 |
Select appropriate tab below to view additional metadata details:
Combined analysis:
Analysis ID | AN002775 | AN002776 |
---|---|---|
Analysis type | MS | MS |
Chromatography type | None (Direct infusion) | None (Direct infusion) |
Chromatography system | Sciex TripleTOF 5600 | Sciex TripleTOF 5600 |
Column | none | none |
MS Type | ESI | ESI |
MS instrument type | QTOF | QTOF |
MS instrument name | ABI Sciex 5600 TripleTOF | ABI Sciex 5600 TripleTOF |
Ion Mode | POSITIVE | NEGATIVE |
Units | m/z | m/z |
Chromatography:
Chromatography ID: | CH002055 |
Chromatography Summary: | Direct infusion |
Instrument Name: | Sciex TripleTOF 5600 |
Column Name: | none |
Chromatography Type: | None (Direct infusion) |