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.

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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 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 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:


Project:

Project ID:PR001090
Project DOI:doi: 10.21228/M8T12F
Project Title:Sclerostin antibody increases trabecular bone and bone mechanical properties by increasing osteoblast activity damaged by whole-body irradiation in mice
Project Type:Proteomics and Lipidomics basic research
Project Summary:A mouse model study to test the hypothesis that treatment with anti-sclerostin antibody (Scl-Ab) would attenuate the adverse effects of irradiation by increasing bone volume and decreasing BM adipose tissue (BMAT), resulting in better quality bone.
Institute:Mainehealth
Last Name:Vary
First Name:Calvin
Address:81 Research Drive, Scarborough, ME, USA 04074
Email:varyc@mmc.org
Phone:2073968148
Funding Source:NIH

Subject:

Subject ID:SU001781
Subject Type:Mammal
Subject Species:Mus musculus
Taxonomy ID:10090
Genotype Strain:C57BL/6J
Age Or Age Range:12-17 weeks
Gender:Female

Factors:

Subject type: Mammal; Subject species: Mus musculus (Factor headings shown in green)

mb_sample_id local_sample_id Treatment
SA158357negMSMSALL-SC-D35-IR_C101_1IR Control
SA158358negMSMSALL-SC-D35-IR_C101_2IR Control
SA158359negMSMSALL-SC-D35-IR_C100_2IR Control
SA158360negMSMSALL-SC-D3-IR_C100_2IR Control
SA158361negMSMSALL-SC-D3-IR_C101_2IR Control
SA158362negMSMSALL-SC-D3-IR_C107_1IR Control
SA158363negMSMSALL-SC-D3-IR_C107_2IR Control
SA158364negMSMSALL-SC-D3-IR_C101_1IR Control
SA158365posMSMSALL-SC-D35-IR_C100_1IR Control
SA158366negMSMSALL-SC-D35-IR_C107_2IR Control
SA158367negMSMSALL-SC-D3-IR_C100_1IR Control
SA158368negMSMSALL-SC-D35-IR_C107_1IR Control
SA158369negMSMSALL-SC-D35-IR_C100_1IR Control
SA158370posMSMSALL-SC-D3-IR_C107_1IR Control
SA158371posMSMSALL-SC-D3-IR_C107_2IR Control
SA158372posMSMSALL-SC-D35-IR_C107_1IR Control
SA158373posMSMSALL-SC-D3-IR_C101_2IR Control
SA158374posMSMSALL-SC-D3-IR_C101_1IR Control
SA158375posMSMSALL-SC-D3-IR_C100_1IR Control
SA158376posMSMSALL-SC-D3-IR_C100_2IR Control
SA158377posMSMSALL-SC-D35-IR_C101_2IR Control
SA158378posMSMSALL-SC-D35-IR_C107_2IR Control
SA158379posMSMSALL-SC-D35-IR_C100_2IR Control
SA158380posMSMSALL-SC-D35-IR_C101_1IR Control
SA158333posMSMSALL-SC-D3-IR_C133_2IR + Scl-Ab
SA158334negMSMSALL-SC-D35-IR_C136_2IR + Scl-Ab
SA158335posMSMSALL-SC-D3-IR_C135_1IR + Scl-Ab
SA158336posMSMSALL-SC-D3-IR_C135_2IR + Scl-Ab
SA158337posMSMSALL-SC-D3-IR_C136_1IR + Scl-Ab
SA158338negMSMSALL-SC-D35-IR_C136_1IR + Scl-Ab
SA158339negMSMSALL-SC-D35-IR_C135_2IR + Scl-Ab
SA158340posMSMSALL-SC-D3-IR_C133_1IR + Scl-Ab
SA158341negMSMSALL-SC-D35-IR_C133_1IR + Scl-Ab
SA158342negMSMSALL-SC-D35-IR_C133_2IR + Scl-Ab
SA158343negMSMSALL-SC-D35-IR_C135_1IR + Scl-Ab
SA158344posMSMSALL-SC-D3-IR_C136_2IR + Scl-Ab
SA158345negMSMSALL-SC-D3-IR_C133_1IR + Scl-Ab
SA158346negMSMSALL-SC-D3-IR_C135_1IR + Scl-Ab
SA158347posMSMSALL-SC-D35-IR_C133_1IR + Scl-Ab
SA158348negMSMSALL-SC-D3-IR_C135_2IR + Scl-Ab
SA158349negMSMSALL-SC-D3-IR_C136_1IR + Scl-Ab
SA158350negMSMSALL-SC-D3-IR_C136_2IR + Scl-Ab
SA158351posMSMSALL-SC-D35-IR_C133_2IR + Scl-Ab
SA158352posMSMSALL-SC-D35-IR_C135_1IR + Scl-Ab
SA158353negMSMSALL-SC-D3-IR_C133_2IR + Scl-Ab
SA158354posMSMSALL-SC-D35-IR_C136_1IR + Scl-Ab
SA158355posMSMSALL-SC-D35-IR_C136_2IR + Scl-Ab
SA158356posMSMSALL-SC-D35-IR_C135_2IR + Scl-Ab
SA158405negMSMSALL-SC-D3-IR_SA121_2Non-IR Control
SA158406posMSMSALL-SC-D3-IR_SA123_2Non-IR Control
SA158407negMSMSALL-SC-D3-IR_SA123_1Non-IR Control
SA158408negMSMSALL-SC-D3-IR_SA121_1Non-IR Control
SA158409negMSMSALL-SC-D3-IR_SA127_2Non-IR Control
SA158410posMSMSALL-SC-D3-IR_SA127_2Non-IR Control
SA158411posMSMSALL-SC-D3-IR_SA127_1Non-IR Control
SA158412negMSMSALL-SC-D3-IR_SA127_1Non-IR Control
SA158413negMSMSALL-SC-D3-IR_SA123_2Non-IR Control
SA158414posMSMSALL-SC-D35-IR_SA121_1Non-IR Control
SA158415negMSMSALL-SC-D35-IR_SA121_2Non-IR Control
SA158416negMSMSALL-SC-D35-IR_SA121_1Non-IR Control
SA158417posMSMSALL-SC-D3-IR_SA123_1Non-IR Control
SA158418negMSMSALL-SC-D35-IR_SA123_1Non-IR Control
SA158419negMSMSALL-SC-D35-IR_SA127_1Non-IR Control
SA158420negMSMSALL-SC-D35-IR_SA127_2Non-IR Control
SA158421posMSMSALL-SC-D35-IR_SA127_2Non-IR Control
SA158422posMSMSALL-SC-D35-IR_SA127_1Non-IR Control
SA158423negMSMSALL-SC-D35-IR_SA123_2Non-IR Control
SA158424posMSMSALL-SC-D3-IR_SA121_1Non-IR Control
SA158425posMSMSALL-SC-D35-IR_SA121_2Non-IR Control
SA158426posMSMSALL-SC-D35-IR_SA123_1Non-IR Control
SA158427posMSMSALL-SC-D35-IR_SA123_2Non-IR Control
SA158428posMSMSALL-SC-D3-IR_SA121_2Non-IR Control
SA158381posMSMSALL-SC-D35-IR_SA152_2Non-IR + Scl-Ab
SA158382posMSMSALL-SC-D35-IR_SA152_1Non-IR + Scl-Ab
SA158383negMSMSALL-SC-D35-IR_SA158_1Non-IR + Scl-Ab
SA158384negMSMSALL-SC-D35-IR_SA153_1Non-IR + Scl-Ab
SA158385negMSMSALL-SC-D35-IR_SA153_2Non-IR + Scl-Ab
SA158386negMSMSALL-SC-D35-IR_SA158_2Non-IR + Scl-Ab
SA158387negMSMSALL-SC-D3-IR_SA158_2Non-IR + Scl-Ab
SA158388negMSMSALL-SC-D35-IR_SA152_1Non-IR + Scl-Ab
SA158389negMSMSALL-SC-D3-IR_SA152_1Non-IR + Scl-Ab
SA158390negMSMSALL-SC-D3-IR_SA152_2Non-IR + Scl-Ab
SA158391negMSMSALL-SC-D3-IR_SA153_1Non-IR + Scl-Ab
SA158392negMSMSALL-SC-D3-IR_SA153_2Non-IR + Scl-Ab
SA158393negMSMSALL-SC-D3-IR_SA158_1Non-IR + Scl-Ab
SA158394negMSMSALL-SC-D35-IR_SA152_2Non-IR + Scl-Ab
SA158395posMSMSALL-SC-D3-IR_SA158_2Non-IR + Scl-Ab
SA158396posMSMSALL-SC-D35-IR_SA153_2Non-IR + Scl-Ab
SA158397posMSMSALL-SC-D35-IR_SA158_2Non-IR + Scl-Ab
SA158398posMSMSALL-SC-D3-IR_SA153_2Non-IR + Scl-Ab
SA158399posMSMSALL-SC-D3-IR_SA158_1Non-IR + Scl-Ab
SA158400posMSMSALL-SC-D35-IR_SA153_1Non-IR + Scl-Ab
SA158401posMSMSALL-SC-D35-IR_SA158_1Non-IR + Scl-Ab
SA158402posMSMSALL-SC-D3-IR_SA152_1Non-IR + Scl-Ab
SA158403posMSMSALL-SC-D3-IR_SA152_2Non-IR + Scl-Ab
SA158404posMSMSALL-SC-D3-IR_SA153_1Non-IR + Scl-Ab
Showing results 1 to 96 of 96

Collection:

Collection ID:CO001774
Collection Summary:Lipidomic analyses were performed on mouse serum (n=3) collected through submandibular and terminal blood collections. Blood samples were extracted (10% of total body weight) and allowed to clot for 60 minutes at room temperature at which point the samples were centrifuged for 15 minutes at 12,000 RCF. The upper phase containing serum was transferred to a new, sterile microcentrifuge tube and frozen at -80°C.
Sample Type:Blood (serum)
Collection Method:submandibular and terminal blood collection
Collection Frequency:Day 3 and Day 35
Storage Conditions:-80℃
Collection Vials:sterile microcentrifuge tube
Storage Vials:sterile microcentrifuge tube

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

Sample Preparation:

Sampleprep ID:SP001787
Sampleprep Summary:Three 12 µL serum aliquots per treatment (representative of individual mice) were provided to the MMCRI Proteomics and Lipidomics Core Facility for analysis. The individual samples were sub-divided into technical replicates, which were then averaged together. Lipid extracts were dissolved in methanol/dichloromethane for mass spectrometry (MS) analysis. Lipidomic analyses were completed via 5600 TripleTOF mass spectrometer (Sciex, Framingham, MA) and downstream analyses, including t-tests and principal component analyses (PCAs), were completed utilizing MarkerView Software (Sciex). PCAs were performed with no weighting, Pareto scaling, and supervised data analysis. Lipids were analyzed using a global, bias-free lipid profiling acquisition technique (MS/MSALL).
Processing Storage Conditions:-80℃
Extract Storage:-80℃

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)

MS:

MS ID:MS002572
Analysis ID:AN002775
Instrument Name:ABI Sciex 5600 TripleTOF
Instrument Type:QTOF
MS Type:ESI
MS Comments:Direct infusion positive and negative mode MSMSALL workflow Sciex-LipidView; Sciex-MarkerView
Ion Mode:POSITIVE
  
MS ID:MS002573
Analysis ID:AN002776
Instrument Name:ABI Sciex 5600 TripleTOF
Instrument Type:QTOF
MS Type:ESI
MS Comments:Direct infusion positive and negative mode MSMSALL workflow Sciex-LipidView; Sciex-MarkerView
Ion Mode:NEGATIVE
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