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.

Show all samples  |  Download mwTab file (text)   |  Download mwTab file(JSON)   |  Download data (Contains raw data)
Study IDST001704
Study TitleSclerostin antibody increases trabecular bone and bone mechanical properties by increasing osteoblast activity damaged by whole-body irradiation in mice
Study TypeBasic research
Study SummaryIrradiation 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 ┬ÁCT 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 NameVary
First NameCalvin
Address81 Research Drive, Scarborough, ME, USA 04074
Emailvaryc@mmc.org
Phone2073968148
Submit Date2021-02-10
Raw Data AvailableYes
Raw Data File Type(s).wiff
Analysis Type DetailLC-MS
Release Date2021-03-01
Release Version1
Calvin Vary Calvin Vary
https://dx.doi.org/10.21228/M8T12F
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

Select appropriate tab below to view additional metadata details:


Treatment:

Treatment ID:TR001794
Treatment Summary:Forty female C57BL/6J mice (Jackson Laboratory, Bar Harbor, ME, USA), 12 weeks of age, were randomly split between two cohorts; Irradiated (IR) and Non-Irradiated (Non-IR) (n=20) and were used for all experiments. Two sub-lethal doses of cesium-137 (Cs-137) whole-body irradiation (2x 3 Gy; total of 6 Gy) with an exposure time of 3.72 minutes per mouse (total of 7.44 minutes) were administered 4 hours apart to the IR mice (n=20) on Day 0. Within each cohort, mice were sub-divided into treatment groups; Vehicle and Scl-Ab VI (25 mg/kg) (supplied by Amgen Inc/UCB Pharma) (n=10/per treatment). All mice were administered either a sterile phosphate buffered saline (PBS) vehicle control or Scl-Ab (25 mg/kg), once weekly via subcutaneous injections for a duration of 5 weeks, starting on Day 0. No adverse effects were observed after the administration of Scl-Ab. All experimental studies and procedures involving mice were performed in accordance with protocols approved by the governing Institutional Animal Care and Use Committee (IACUC). Additional Study Design and Drug Treatment information can be found in the Supplemental Material.
Treatment:Neutralizing antibodies to sclerostin (Scl-Ab)
Treatment Compound:Scl-Ab VI (supplied by Amgen Inc/UCB Pharma)
Treatment Route:subcutaneous injections
Treatment Dose:25 mg/kg
Treatment Doseduration:once weekly for 5 weeks
Treatment Vehicle:sterile phosphate buffered saline (PBS) vehicle control
  logo