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:
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 |
|---|---|---|
| SA158357 | negMSMSALL-SC-D35-IR_C101_1 | IR Control |
| SA158358 | negMSMSALL-SC-D35-IR_C101_2 | IR Control |
| SA158359 | negMSMSALL-SC-D35-IR_C100_2 | IR Control |
| SA158360 | negMSMSALL-SC-D3-IR_C100_2 | IR Control |
| SA158361 | negMSMSALL-SC-D3-IR_C101_2 | IR Control |
| SA158362 | negMSMSALL-SC-D3-IR_C107_1 | IR Control |
| SA158363 | negMSMSALL-SC-D3-IR_C107_2 | IR Control |
| SA158364 | negMSMSALL-SC-D3-IR_C101_1 | IR Control |
| SA158365 | posMSMSALL-SC-D35-IR_C100_1 | IR Control |
| SA158366 | negMSMSALL-SC-D35-IR_C107_2 | IR Control |
| SA158367 | negMSMSALL-SC-D3-IR_C100_1 | IR Control |
| SA158368 | negMSMSALL-SC-D35-IR_C107_1 | IR Control |
| SA158369 | negMSMSALL-SC-D35-IR_C100_1 | IR Control |
| SA158370 | posMSMSALL-SC-D3-IR_C107_1 | IR Control |
| SA158371 | posMSMSALL-SC-D3-IR_C107_2 | IR Control |
| SA158372 | posMSMSALL-SC-D35-IR_C107_1 | IR Control |
| SA158373 | posMSMSALL-SC-D3-IR_C101_2 | IR Control |
| SA158374 | posMSMSALL-SC-D3-IR_C101_1 | IR Control |
| SA158375 | posMSMSALL-SC-D3-IR_C100_1 | IR Control |
| SA158376 | posMSMSALL-SC-D3-IR_C100_2 | IR Control |
| SA158377 | posMSMSALL-SC-D35-IR_C101_2 | IR Control |
| SA158378 | posMSMSALL-SC-D35-IR_C107_2 | IR Control |
| SA158379 | posMSMSALL-SC-D35-IR_C100_2 | IR Control |
| SA158380 | posMSMSALL-SC-D35-IR_C101_1 | IR Control |
| SA158333 | posMSMSALL-SC-D3-IR_C133_2 | IR + Scl-Ab |
| SA158334 | negMSMSALL-SC-D35-IR_C136_2 | IR + Scl-Ab |
| SA158335 | posMSMSALL-SC-D3-IR_C135_1 | IR + Scl-Ab |
| SA158336 | posMSMSALL-SC-D3-IR_C135_2 | IR + Scl-Ab |
| SA158337 | posMSMSALL-SC-D3-IR_C136_1 | IR + Scl-Ab |
| SA158338 | negMSMSALL-SC-D35-IR_C136_1 | IR + Scl-Ab |
| SA158339 | negMSMSALL-SC-D35-IR_C135_2 | IR + Scl-Ab |
| SA158340 | posMSMSALL-SC-D3-IR_C133_1 | IR + Scl-Ab |
| SA158341 | negMSMSALL-SC-D35-IR_C133_1 | IR + Scl-Ab |
| SA158342 | negMSMSALL-SC-D35-IR_C133_2 | IR + Scl-Ab |
| SA158343 | negMSMSALL-SC-D35-IR_C135_1 | IR + Scl-Ab |
| SA158344 | posMSMSALL-SC-D3-IR_C136_2 | IR + Scl-Ab |
| SA158345 | negMSMSALL-SC-D3-IR_C133_1 | IR + Scl-Ab |
| SA158346 | negMSMSALL-SC-D3-IR_C135_1 | IR + Scl-Ab |
| SA158347 | posMSMSALL-SC-D35-IR_C133_1 | IR + Scl-Ab |
| SA158348 | negMSMSALL-SC-D3-IR_C135_2 | IR + Scl-Ab |
| SA158349 | negMSMSALL-SC-D3-IR_C136_1 | IR + Scl-Ab |
| SA158350 | negMSMSALL-SC-D3-IR_C136_2 | IR + Scl-Ab |
| SA158351 | posMSMSALL-SC-D35-IR_C133_2 | IR + Scl-Ab |
| SA158352 | posMSMSALL-SC-D35-IR_C135_1 | IR + Scl-Ab |
| SA158353 | negMSMSALL-SC-D3-IR_C133_2 | IR + Scl-Ab |
| SA158354 | posMSMSALL-SC-D35-IR_C136_1 | IR + Scl-Ab |
| SA158355 | posMSMSALL-SC-D35-IR_C136_2 | IR + Scl-Ab |
| SA158356 | posMSMSALL-SC-D35-IR_C135_2 | IR + Scl-Ab |
| SA158405 | negMSMSALL-SC-D3-IR_SA121_2 | Non-IR Control |
| SA158406 | posMSMSALL-SC-D3-IR_SA123_2 | Non-IR Control |
| SA158407 | negMSMSALL-SC-D3-IR_SA123_1 | Non-IR Control |
| SA158408 | negMSMSALL-SC-D3-IR_SA121_1 | Non-IR Control |
| SA158409 | negMSMSALL-SC-D3-IR_SA127_2 | Non-IR Control |
| SA158410 | posMSMSALL-SC-D3-IR_SA127_2 | Non-IR Control |
| SA158411 | posMSMSALL-SC-D3-IR_SA127_1 | Non-IR Control |
| SA158412 | negMSMSALL-SC-D3-IR_SA127_1 | Non-IR Control |
| SA158413 | negMSMSALL-SC-D3-IR_SA123_2 | Non-IR Control |
| SA158414 | posMSMSALL-SC-D35-IR_SA121_1 | Non-IR Control |
| SA158415 | negMSMSALL-SC-D35-IR_SA121_2 | Non-IR Control |
| SA158416 | negMSMSALL-SC-D35-IR_SA121_1 | Non-IR Control |
| SA158417 | posMSMSALL-SC-D3-IR_SA123_1 | Non-IR Control |
| SA158418 | negMSMSALL-SC-D35-IR_SA123_1 | Non-IR Control |
| SA158419 | negMSMSALL-SC-D35-IR_SA127_1 | Non-IR Control |
| SA158420 | negMSMSALL-SC-D35-IR_SA127_2 | Non-IR Control |
| SA158421 | posMSMSALL-SC-D35-IR_SA127_2 | Non-IR Control |
| SA158422 | posMSMSALL-SC-D35-IR_SA127_1 | Non-IR Control |
| SA158423 | negMSMSALL-SC-D35-IR_SA123_2 | Non-IR Control |
| SA158424 | posMSMSALL-SC-D3-IR_SA121_1 | Non-IR Control |
| SA158425 | posMSMSALL-SC-D35-IR_SA121_2 | Non-IR Control |
| SA158426 | posMSMSALL-SC-D35-IR_SA123_1 | Non-IR Control |
| SA158427 | posMSMSALL-SC-D35-IR_SA123_2 | Non-IR Control |
| SA158428 | posMSMSALL-SC-D3-IR_SA121_2 | Non-IR Control |
| SA158381 | posMSMSALL-SC-D35-IR_SA152_2 | Non-IR + Scl-Ab |
| SA158382 | posMSMSALL-SC-D35-IR_SA152_1 | Non-IR + Scl-Ab |
| SA158383 | negMSMSALL-SC-D35-IR_SA158_1 | Non-IR + Scl-Ab |
| SA158384 | negMSMSALL-SC-D35-IR_SA153_1 | Non-IR + Scl-Ab |
| SA158385 | negMSMSALL-SC-D35-IR_SA153_2 | Non-IR + Scl-Ab |
| SA158386 | negMSMSALL-SC-D35-IR_SA158_2 | Non-IR + Scl-Ab |
| SA158387 | negMSMSALL-SC-D3-IR_SA158_2 | Non-IR + Scl-Ab |
| SA158388 | negMSMSALL-SC-D35-IR_SA152_1 | Non-IR + Scl-Ab |
| SA158389 | negMSMSALL-SC-D3-IR_SA152_1 | Non-IR + Scl-Ab |
| SA158390 | negMSMSALL-SC-D3-IR_SA152_2 | Non-IR + Scl-Ab |
| SA158391 | negMSMSALL-SC-D3-IR_SA153_1 | Non-IR + Scl-Ab |
| SA158392 | negMSMSALL-SC-D3-IR_SA153_2 | Non-IR + Scl-Ab |
| SA158393 | negMSMSALL-SC-D3-IR_SA158_1 | Non-IR + Scl-Ab |
| SA158394 | negMSMSALL-SC-D35-IR_SA152_2 | Non-IR + Scl-Ab |
| SA158395 | posMSMSALL-SC-D3-IR_SA158_2 | Non-IR + Scl-Ab |
| SA158396 | posMSMSALL-SC-D35-IR_SA153_2 | Non-IR + Scl-Ab |
| SA158397 | posMSMSALL-SC-D35-IR_SA158_2 | Non-IR + Scl-Ab |
| SA158398 | posMSMSALL-SC-D3-IR_SA153_2 | Non-IR + Scl-Ab |
| SA158399 | posMSMSALL-SC-D3-IR_SA158_1 | Non-IR + Scl-Ab |
| SA158400 | posMSMSALL-SC-D35-IR_SA153_1 | Non-IR + Scl-Ab |
| SA158401 | posMSMSALL-SC-D35-IR_SA158_1 | Non-IR + Scl-Ab |
| SA158402 | posMSMSALL-SC-D3-IR_SA152_1 | Non-IR + Scl-Ab |
| SA158403 | posMSMSALL-SC-D3-IR_SA152_2 | Non-IR + Scl-Ab |
| SA158404 | posMSMSALL-SC-D3-IR_SA153_1 | Non-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 | Triple TOF | Triple TOF |
| 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: | Triple TOF |
| 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: | Triple TOF |
| MS Type: | ESI |
| MS Comments: | Direct infusion positive and negative mode MSMSALL workflow Sciex-LipidView; Sciex-MarkerView |
| Ion Mode: | NEGATIVE |
