#METABOLOMICS WORKBENCH varyc_20210210_112150 DATATRACK_ID:2470 STUDY_ID:ST001704 ANALYSIS_ID:AN002776 PROJECT_ID:PR001090 VERSION 1 CREATED_ON February 17, 2021, 1:40 pm #PROJECT PR:PROJECT_TITLE Sclerostin antibody increases trabecular bone and bone mechanical properties by PR:PROJECT_TITLE increasing osteoblast activity damaged by whole-body irradiation in mice PR:PROJECT_TYPE Proteomics and Lipidomics basic research PR:PROJECT_SUMMARY A mouse model study to test the hypothesis that treatment with anti-sclerostin PR:PROJECT_SUMMARY antibody (Scl-Ab) would attenuate the adverse effects of irradiation by PR:PROJECT_SUMMARY increasing bone volume and decreasing BM adipose tissue (BMAT), resulting in PR:PROJECT_SUMMARY better quality bone. PR:INSTITUTE Mainehealth PR:LAST_NAME Vary PR:FIRST_NAME Calvin PR:ADDRESS 81 Research Drive, Scarborough, ME, USA 04074 PR:EMAIL varyc@mmc.org PR:PHONE 2073968148 PR:FUNDING_SOURCE NIH #STUDY ST:STUDY_TITLE Sclerostin antibody increases trabecular bone and bone mechanical properties by ST:STUDY_TITLE increasing osteoblast activity damaged by whole-body irradiation in mice ST:STUDY_TYPE Basic research ST:STUDY_SUMMARY Irradiation therapy causes bone deterioration and increased risk for ST:STUDY_SUMMARY skeletal-related events. Irradiation interferes with trabecular architecture ST:STUDY_SUMMARY through increased osteoclastic activity, decreased osteoblastic activity, and ST:STUDY_SUMMARY increased adipocyte expansion in the bone marrow (BM), which further compounds ST:STUDY_SUMMARY bone-related disease. Neutralizing antibodies to sclerostin (Scl-Ab) increase ST:STUDY_SUMMARY bone mass and strength by increasing bone formation and reducing bone ST:STUDY_SUMMARY resorption. We hypothesized that treatment with Scl-Ab would attenuate the ST:STUDY_SUMMARY adverse effects of irradiation by increasing bone volume and decreasing BM ST:STUDY_SUMMARY adipose tissue (BMAT), resulting in better quality bone. In this study, ST:STUDY_SUMMARY 12-week-old female C57BL/6J mice were exposed to 6 Gy whole-body irradiation or ST:STUDY_SUMMARY were non-irradiated, then administered Scl-Ab (25 mg/kg) or vehicle weekly for 5 ST:STUDY_SUMMARY weeks. Femoral µCT analysis confirmed that the overall effect of IR ST:STUDY_SUMMARY significantly decreased trabecular bone volume/total volume (Tb.BV/TV) (2-way ST:STUDY_SUMMARY ANOVA, p<0.0001) with a -43.8% loss in Tb.BV/TV in the IR control group. Scl-Ab ST:STUDY_SUMMARY independently increased Tb.BV/TV by 3.07-fold in non-irradiated and 3.6-fold in ST:STUDY_SUMMARY irradiated mice (2-way ANOVA, p<0.0001). Irradiation did not affect cortical ST:STUDY_SUMMARY parameters, although Scl-Ab increased cortical thickness and area significantly ST:STUDY_SUMMARY in both irradiated and non-irradiated mice (2-way ANOVA, p<0.0001). Femoral ST:STUDY_SUMMARY mechanical testing confirmed Scl-Ab significantly increased bending rigidity and ST:STUDY_SUMMARY ultimate moment independently of irradiation (2-way ANOVA, p<0.0001). Static and ST:STUDY_SUMMARY dynamic histomorphometry of the femoral metaphysis revealed osteoblast vigor, ST:STUDY_SUMMARY not number, was significantly increased in the irradiated mice treated with ST:STUDY_SUMMARY Scl-Ab. Systemic alterations were assessed through serum lipidomic analysis, ST:STUDY_SUMMARY which showed that Scl-Ab normalized lipid profiles in the irradiated group. This ST:STUDY_SUMMARY data supports the theory of sclerostin as a novel contributor to the regulation ST:STUDY_SUMMARY of osteoblast activity after irradiation. Overall, our data support the ST:STUDY_SUMMARY hypothesis that Scl-Ab ameliorates the deleterious effects of whole-body ST:STUDY_SUMMARY irradiation on bone and adipose tissue in a mouse model. Our findings suggest ST:STUDY_SUMMARY that future research into localized and systemic therapies after irradiation ST:STUDY_SUMMARY exposure is warranted. ST:INSTITUTE Mainehealth ST:LAST_NAME Vary ST:FIRST_NAME Calvin ST:ADDRESS 81 Research Drive ST:EMAIL varyc@mmc.org ST:PHONE 2073968148 #SUBJECT SU:SUBJECT_TYPE Mammal SU:SUBJECT_SPECIES Mus musculus SU:TAXONOMY_ID 10090 SU:GENOTYPE_STRAIN C57BL/6J SU:AGE_OR_AGE_RANGE 12-17 weeks SU:GENDER Female #SUBJECT_SAMPLE_FACTORS: SUBJECT(optional)[tab]SAMPLE[tab]FACTORS(NAME:VALUE pairs separated by |)[tab]Raw file names and additional sample data SUBJECT_SAMPLE_FACTORS - posMSMSALL-SC-D35-IR_C100_1 Treatment:IR Control Strain=C57BL/6J; RAW_FILE_NAME=posMSMSALL-SC-D35-IR_C100_1 SUBJECT_SAMPLE_FACTORS - posMSMSALL-SC-D35-IR_C100_2 Treatment:IR Control Strain=C57BL/6J; RAW_FILE_NAME=posMSMSALL-SC-D35-IR_C100_2 SUBJECT_SAMPLE_FACTORS - posMSMSALL-SC-D35-IR_C101_1 Treatment:IR Control Strain=C57BL/6J; RAW_FILE_NAME=posMSMSALL-SC-D35-IR_C101_1 SUBJECT_SAMPLE_FACTORS - posMSMSALL-SC-D35-IR_C101_2 Treatment:IR Control Strain=C57BL/6J; RAW_FILE_NAME=posMSMSALL-SC-D35-IR_C101_2 SUBJECT_SAMPLE_FACTORS - posMSMSALL-SC-D35-IR_C107_1 Treatment:IR Control Strain=C57BL/6J; RAW_FILE_NAME=posMSMSALL-SC-D35-IR_C107_1 SUBJECT_SAMPLE_FACTORS - posMSMSALL-SC-D35-IR_C107_2 Treatment:IR Control Strain=C57BL/6J; RAW_FILE_NAME=posMSMSALL-SC-D35-IR_C107_2 SUBJECT_SAMPLE_FACTORS - posMSMSALL-SC-D35-IR_C133_1 Treatment:IR + Scl-Ab Strain=C57BL/6J; RAW_FILE_NAME=posMSMSALL-SC-D35-IR_C133_1 SUBJECT_SAMPLE_FACTORS - posMSMSALL-SC-D35-IR_C133_2 Treatment:IR + Scl-Ab Strain=C57BL/6J; RAW_FILE_NAME=posMSMSALL-SC-D35-IR_C133_2 SUBJECT_SAMPLE_FACTORS - posMSMSALL-SC-D35-IR_C135_1 Treatment:IR + Scl-Ab Strain=C57BL/6J; RAW_FILE_NAME=posMSMSALL-SC-D35-IR_C135_1 SUBJECT_SAMPLE_FACTORS - posMSMSALL-SC-D35-IR_C135_2 Treatment:IR + Scl-Ab Strain=C57BL/6J; RAW_FILE_NAME=posMSMSALL-SC-D35-IR_C135_2 SUBJECT_SAMPLE_FACTORS - posMSMSALL-SC-D35-IR_C136_1 Treatment:IR + Scl-Ab Strain=C57BL/6J; RAW_FILE_NAME=posMSMSALL-SC-D35-IR_C136_1 SUBJECT_SAMPLE_FACTORS - posMSMSALL-SC-D35-IR_C136_2 Treatment:IR + Scl-Ab Strain=C57BL/6J; RAW_FILE_NAME=posMSMSALL-SC-D35-IR_C136_2 SUBJECT_SAMPLE_FACTORS - posMSMSALL-SC-D35-IR_SA121_1 Treatment:Non-IR Control Strain=C57BL/6J; RAW_FILE_NAME=posMSMSALL-SC-D35-IR_SA121_1 SUBJECT_SAMPLE_FACTORS - posMSMSALL-SC-D35-IR_SA121_2 Treatment:Non-IR Control Strain=C57BL/6J; RAW_FILE_NAME=posMSMSALL-SC-D35-IR_SA121_2 SUBJECT_SAMPLE_FACTORS - posMSMSALL-SC-D35-IR_SA123_1 Treatment:Non-IR Control Strain=C57BL/6J; RAW_FILE_NAME=posMSMSALL-SC-D35-IR_SA123_1 SUBJECT_SAMPLE_FACTORS - posMSMSALL-SC-D35-IR_SA123_2 Treatment:Non-IR Control Strain=C57BL/6J; RAW_FILE_NAME=posMSMSALL-SC-D35-IR_SA123_2 SUBJECT_SAMPLE_FACTORS - posMSMSALL-SC-D35-IR_SA127_1 Treatment:Non-IR Control Strain=C57BL/6J; RAW_FILE_NAME=posMSMSALL-SC-D35-IR_SA127_1 SUBJECT_SAMPLE_FACTORS - posMSMSALL-SC-D35-IR_SA127_2 Treatment:Non-IR Control Strain=C57BL/6J; RAW_FILE_NAME=posMSMSALL-SC-D35-IR_SA127_2 SUBJECT_SAMPLE_FACTORS - posMSMSALL-SC-D35-IR_SA152_1 Treatment:Non-IR + Scl-Ab Strain=C57BL/6J; RAW_FILE_NAME=posMSMSALL-SC-D35-IR_SA152_1 SUBJECT_SAMPLE_FACTORS - posMSMSALL-SC-D35-IR_SA152_2 Treatment:Non-IR + Scl-Ab Strain=C57BL/6J; RAW_FILE_NAME=posMSMSALL-SC-D35-IR_SA152_2 SUBJECT_SAMPLE_FACTORS - posMSMSALL-SC-D35-IR_SA153_1 Treatment:Non-IR + Scl-Ab Strain=C57BL/6J; RAW_FILE_NAME=posMSMSALL-SC-D35-IR_SA153_1 SUBJECT_SAMPLE_FACTORS - posMSMSALL-SC-D35-IR_SA153_2 Treatment:Non-IR + Scl-Ab Strain=C57BL/6J; RAW_FILE_NAME=posMSMSALL-SC-D35-IR_SA153_2 SUBJECT_SAMPLE_FACTORS - posMSMSALL-SC-D35-IR_SA158_1 Treatment:Non-IR + Scl-Ab Strain=C57BL/6J; RAW_FILE_NAME=posMSMSALL-SC-D35-IR_SA158_1 SUBJECT_SAMPLE_FACTORS - posMSMSALL-SC-D35-IR_SA158_2 Treatment:Non-IR + Scl-Ab Strain=C57BL/6J; RAW_FILE_NAME=posMSMSALL-SC-D35-IR_SA158_2 SUBJECT_SAMPLE_FACTORS - posMSMSALL-SC-D3-IR_C100_1 Treatment:IR Control Strain=C57BL/6J; RAW_FILE_NAME=posMSMSALL-SC-D3-IR_C100_1 SUBJECT_SAMPLE_FACTORS - posMSMSALL-SC-D3-IR_C100_2 Treatment:IR Control Strain=C57BL/6J; RAW_FILE_NAME=posMSMSALL-SC-D3-IR_C100_2 SUBJECT_SAMPLE_FACTORS - posMSMSALL-SC-D3-IR_C101_1 Treatment:IR Control Strain=C57BL/6J; RAW_FILE_NAME=posMSMSALL-SC-D3-IR_C101_1 SUBJECT_SAMPLE_FACTORS - posMSMSALL-SC-D3-IR_C101_2 Treatment:IR Control Strain=C57BL/6J; RAW_FILE_NAME=posMSMSALL-SC-D3-IR_C101_2 SUBJECT_SAMPLE_FACTORS - posMSMSALL-SC-D3-IR_C107_1 Treatment:IR Control Strain=C57BL/6J; RAW_FILE_NAME=posMSMSALL-SC-D3-IR_C107_1 SUBJECT_SAMPLE_FACTORS - posMSMSALL-SC-D3-IR_C107_2 Treatment:IR Control Strain=C57BL/6J; RAW_FILE_NAME=posMSMSALL-SC-D3-IR_C107_2 SUBJECT_SAMPLE_FACTORS - posMSMSALL-SC-D3-IR_C133_1 Treatment:IR + Scl-Ab Strain=C57BL/6J; RAW_FILE_NAME=posMSMSALL-SC-D3-IR_C133_1 SUBJECT_SAMPLE_FACTORS - posMSMSALL-SC-D3-IR_C133_2 Treatment:IR + Scl-Ab Strain=C57BL/6J; RAW_FILE_NAME=posMSMSALL-SC-D3-IR_C133_2 SUBJECT_SAMPLE_FACTORS - posMSMSALL-SC-D3-IR_C135_1 Treatment:IR + Scl-Ab Strain=C57BL/6J; RAW_FILE_NAME=posMSMSALL-SC-D3-IR_C135_1 SUBJECT_SAMPLE_FACTORS - posMSMSALL-SC-D3-IR_C135_2 Treatment:IR + Scl-Ab Strain=C57BL/6J; RAW_FILE_NAME=posMSMSALL-SC-D3-IR_C135_2 SUBJECT_SAMPLE_FACTORS - posMSMSALL-SC-D3-IR_C136_1 Treatment:IR + Scl-Ab Strain=C57BL/6J; RAW_FILE_NAME=posMSMSALL-SC-D3-IR_C136_1 SUBJECT_SAMPLE_FACTORS - posMSMSALL-SC-D3-IR_C136_2 Treatment:IR + Scl-Ab Strain=C57BL/6J; RAW_FILE_NAME=posMSMSALL-SC-D3-IR_C136_2 SUBJECT_SAMPLE_FACTORS - posMSMSALL-SC-D3-IR_SA121_1 Treatment:Non-IR Control Strain=C57BL/6J; RAW_FILE_NAME=posMSMSALL-SC-D3-IR_SA121_1 SUBJECT_SAMPLE_FACTORS - posMSMSALL-SC-D3-IR_SA121_2 Treatment:Non-IR Control Strain=C57BL/6J; RAW_FILE_NAME=posMSMSALL-SC-D3-IR_SA121_2 SUBJECT_SAMPLE_FACTORS - posMSMSALL-SC-D3-IR_SA123_1 Treatment:Non-IR Control Strain=C57BL/6J; RAW_FILE_NAME=posMSMSALL-SC-D3-IR_SA123_1 SUBJECT_SAMPLE_FACTORS - posMSMSALL-SC-D3-IR_SA123_2 Treatment:Non-IR Control Strain=C57BL/6J; RAW_FILE_NAME=posMSMSALL-SC-D3-IR_SA123_2 SUBJECT_SAMPLE_FACTORS - posMSMSALL-SC-D3-IR_SA127_1 Treatment:Non-IR Control Strain=C57BL/6J; RAW_FILE_NAME=posMSMSALL-SC-D3-IR_SA127_1 SUBJECT_SAMPLE_FACTORS - posMSMSALL-SC-D3-IR_SA127_2 Treatment:Non-IR Control Strain=C57BL/6J; RAW_FILE_NAME=posMSMSALL-SC-D3-IR_SA127_2 SUBJECT_SAMPLE_FACTORS - posMSMSALL-SC-D3-IR_SA152_1 Treatment:Non-IR + Scl-Ab Strain=C57BL/6J; RAW_FILE_NAME=posMSMSALL-SC-D3-IR_SA152_1 SUBJECT_SAMPLE_FACTORS - posMSMSALL-SC-D3-IR_SA152_2 Treatment:Non-IR + Scl-Ab Strain=C57BL/6J; RAW_FILE_NAME=posMSMSALL-SC-D3-IR_SA152_2 SUBJECT_SAMPLE_FACTORS - posMSMSALL-SC-D3-IR_SA153_1 Treatment:Non-IR + Scl-Ab Strain=C57BL/6J; RAW_FILE_NAME=posMSMSALL-SC-D3-IR_SA153_1 SUBJECT_SAMPLE_FACTORS - posMSMSALL-SC-D3-IR_SA153_2 Treatment:Non-IR + Scl-Ab Strain=C57BL/6J; RAW_FILE_NAME=posMSMSALL-SC-D3-IR_SA153_2 SUBJECT_SAMPLE_FACTORS - posMSMSALL-SC-D3-IR_SA158_1 Treatment:Non-IR + Scl-Ab Strain=C57BL/6J; RAW_FILE_NAME=posMSMSALL-SC-D3-IR_SA158_1 SUBJECT_SAMPLE_FACTORS - posMSMSALL-SC-D3-IR_SA158_2 Treatment:Non-IR + Scl-Ab Strain=C57BL/6J; RAW_FILE_NAME=posMSMSALL-SC-D3-IR_SA158_2 SUBJECT_SAMPLE_FACTORS - negMSMSALL-SC-D35-IR_C100_1 Treatment:IR Control Strain=C57BL/6J; RAW_FILE_NAME=negMSMSALL-SC-D35-IR_C100_1 SUBJECT_SAMPLE_FACTORS - negMSMSALL-SC-D35-IR_C100_2 Treatment:IR Control Strain=C57BL/6J; RAW_FILE_NAME=negMSMSALL-SC-D35-IR_C100_2 SUBJECT_SAMPLE_FACTORS - negMSMSALL-SC-D35-IR_C101_1 Treatment:IR Control Strain=C57BL/6J; RAW_FILE_NAME=negMSMSALL-SC-D35-IR_C101_1 SUBJECT_SAMPLE_FACTORS - negMSMSALL-SC-D35-IR_C101_2 Treatment:IR Control Strain=C57BL/6J; RAW_FILE_NAME=negMSMSALL-SC-D35-IR_C101_2 SUBJECT_SAMPLE_FACTORS - negMSMSALL-SC-D35-IR_C107_1 Treatment:IR Control Strain=C57BL/6J; RAW_FILE_NAME=negMSMSALL-SC-D35-IR_C107_1 SUBJECT_SAMPLE_FACTORS - negMSMSALL-SC-D35-IR_C107_2 Treatment:IR Control Strain=C57BL/6J; RAW_FILE_NAME=negMSMSALL-SC-D35-IR_C107_2 SUBJECT_SAMPLE_FACTORS - negMSMSALL-SC-D35-IR_C133_1 Treatment:IR + Scl-Ab Strain=C57BL/6J; RAW_FILE_NAME=negMSMSALL-SC-D35-IR_C133_1 SUBJECT_SAMPLE_FACTORS - negMSMSALL-SC-D35-IR_C133_2 Treatment:IR + Scl-Ab Strain=C57BL/6J; RAW_FILE_NAME=negMSMSALL-SC-D35-IR_C133_2 SUBJECT_SAMPLE_FACTORS - negMSMSALL-SC-D35-IR_C135_1 Treatment:IR + Scl-Ab Strain=C57BL/6J; RAW_FILE_NAME=negMSMSALL-SC-D35-IR_C135_1 SUBJECT_SAMPLE_FACTORS - negMSMSALL-SC-D35-IR_C135_2 Treatment:IR + Scl-Ab Strain=C57BL/6J; RAW_FILE_NAME=negMSMSALL-SC-D35-IR_C135_2 SUBJECT_SAMPLE_FACTORS - negMSMSALL-SC-D35-IR_C136_1 Treatment:IR + Scl-Ab Strain=C57BL/6J; RAW_FILE_NAME=negMSMSALL-SC-D35-IR_C136_1 SUBJECT_SAMPLE_FACTORS - negMSMSALL-SC-D35-IR_C136_2 Treatment:IR + Scl-Ab Strain=C57BL/6J; RAW_FILE_NAME=negMSMSALL-SC-D35-IR_C136_2 SUBJECT_SAMPLE_FACTORS - negMSMSALL-SC-D35-IR_SA121_1 Treatment:Non-IR Control Strain=C57BL/6J; RAW_FILE_NAME=negMSMSALL-SC-D35-IR_SA121_1 SUBJECT_SAMPLE_FACTORS - negMSMSALL-SC-D35-IR_SA121_2 Treatment:Non-IR Control Strain=C57BL/6J; RAW_FILE_NAME=negMSMSALL-SC-D35-IR_SA121_2 SUBJECT_SAMPLE_FACTORS - negMSMSALL-SC-D35-IR_SA123_1 Treatment:Non-IR Control Strain=C57BL/6J; RAW_FILE_NAME=negMSMSALL-SC-D35-IR_SA123_1 SUBJECT_SAMPLE_FACTORS - negMSMSALL-SC-D35-IR_SA123_2 Treatment:Non-IR Control Strain=C57BL/6J; RAW_FILE_NAME=negMSMSALL-SC-D35-IR_SA123_2 SUBJECT_SAMPLE_FACTORS - negMSMSALL-SC-D35-IR_SA127_1 Treatment:Non-IR Control Strain=C57BL/6J; RAW_FILE_NAME=negMSMSALL-SC-D35-IR_SA127_1 SUBJECT_SAMPLE_FACTORS - negMSMSALL-SC-D35-IR_SA127_2 Treatment:Non-IR Control Strain=C57BL/6J; RAW_FILE_NAME=negMSMSALL-SC-D35-IR_SA127_2 SUBJECT_SAMPLE_FACTORS - negMSMSALL-SC-D35-IR_SA152_1 Treatment:Non-IR + Scl-Ab Strain=C57BL/6J; RAW_FILE_NAME=negMSMSALL-SC-D35-IR_SA152_1 SUBJECT_SAMPLE_FACTORS - negMSMSALL-SC-D35-IR_SA152_2 Treatment:Non-IR + Scl-Ab Strain=C57BL/6J; RAW_FILE_NAME=negMSMSALL-SC-D35-IR_SA152_2 SUBJECT_SAMPLE_FACTORS - negMSMSALL-SC-D35-IR_SA153_1 Treatment:Non-IR + Scl-Ab Strain=C57BL/6J; RAW_FILE_NAME=negMSMSALL-SC-D35-IR_SA153_1 SUBJECT_SAMPLE_FACTORS - negMSMSALL-SC-D35-IR_SA153_2 Treatment:Non-IR + Scl-Ab Strain=C57BL/6J; RAW_FILE_NAME=negMSMSALL-SC-D35-IR_SA153_2 SUBJECT_SAMPLE_FACTORS - negMSMSALL-SC-D35-IR_SA158_1 Treatment:Non-IR + Scl-Ab Strain=C57BL/6J; RAW_FILE_NAME=negMSMSALL-SC-D35-IR_SA158_1 SUBJECT_SAMPLE_FACTORS - negMSMSALL-SC-D35-IR_SA158_2 Treatment:Non-IR + Scl-Ab Strain=C57BL/6J; RAW_FILE_NAME=negMSMSALL-SC-D35-IR_SA158_2 SUBJECT_SAMPLE_FACTORS - negMSMSALL-SC-D3-IR_C100_1 Treatment:IR Control Strain=C57BL/6J; RAW_FILE_NAME=negMSMSALL-SC-D3-IR_C100_1 SUBJECT_SAMPLE_FACTORS - negMSMSALL-SC-D3-IR_C100_2 Treatment:IR Control Strain=C57BL/6J; RAW_FILE_NAME=negMSMSALL-SC-D3-IR_C100_2 SUBJECT_SAMPLE_FACTORS - negMSMSALL-SC-D3-IR_C101_1 Treatment:IR Control Strain=C57BL/6J; RAW_FILE_NAME=negMSMSALL-SC-D3-IR_C101_1 SUBJECT_SAMPLE_FACTORS - negMSMSALL-SC-D3-IR_C101_2 Treatment:IR Control Strain=C57BL/6J; RAW_FILE_NAME=negMSMSALL-SC-D3-IR_C101_2 SUBJECT_SAMPLE_FACTORS - negMSMSALL-SC-D3-IR_C107_1 Treatment:IR Control Strain=C57BL/6J; RAW_FILE_NAME=negMSMSALL-SC-D3-IR_C107_1 SUBJECT_SAMPLE_FACTORS - negMSMSALL-SC-D3-IR_C107_2 Treatment:IR Control Strain=C57BL/6J; RAW_FILE_NAME=negMSMSALL-SC-D3-IR_C107_2 SUBJECT_SAMPLE_FACTORS - negMSMSALL-SC-D3-IR_C133_1 Treatment:IR + Scl-Ab Strain=C57BL/6J; RAW_FILE_NAME=negMSMSALL-SC-D3-IR_C133_1 SUBJECT_SAMPLE_FACTORS - negMSMSALL-SC-D3-IR_C133_2 Treatment:IR + Scl-Ab Strain=C57BL/6J; RAW_FILE_NAME=negMSMSALL-SC-D3-IR_C133_2 SUBJECT_SAMPLE_FACTORS - negMSMSALL-SC-D3-IR_C135_1 Treatment:IR + Scl-Ab Strain=C57BL/6J; RAW_FILE_NAME=negMSMSALL-SC-D3-IR_C135_1 SUBJECT_SAMPLE_FACTORS - negMSMSALL-SC-D3-IR_C135_2 Treatment:IR + Scl-Ab Strain=C57BL/6J; RAW_FILE_NAME=negMSMSALL-SC-D3-IR_C135_2 SUBJECT_SAMPLE_FACTORS - negMSMSALL-SC-D3-IR_C136_1 Treatment:IR + Scl-Ab Strain=C57BL/6J; RAW_FILE_NAME=negMSMSALL-SC-D3-IR_C136_1 SUBJECT_SAMPLE_FACTORS - negMSMSALL-SC-D3-IR_C136_2 Treatment:IR + Scl-Ab Strain=C57BL/6J; RAW_FILE_NAME=negMSMSALL-SC-D3-IR_C136_2 SUBJECT_SAMPLE_FACTORS - negMSMSALL-SC-D3-IR_SA121_1 Treatment:Non-IR Control Strain=C57BL/6J; RAW_FILE_NAME=negMSMSALL-SC-D3-IR_SA121_1 SUBJECT_SAMPLE_FACTORS - negMSMSALL-SC-D3-IR_SA121_2 Treatment:Non-IR Control Strain=C57BL/6J; RAW_FILE_NAME=negMSMSALL-SC-D3-IR_SA121_2 SUBJECT_SAMPLE_FACTORS - negMSMSALL-SC-D3-IR_SA123_1 Treatment:Non-IR Control Strain=C57BL/6J; RAW_FILE_NAME=negMSMSALL-SC-D3-IR_SA123_1 SUBJECT_SAMPLE_FACTORS - negMSMSALL-SC-D3-IR_SA123_2 Treatment:Non-IR Control Strain=C57BL/6J; RAW_FILE_NAME=negMSMSALL-SC-D3-IR_SA123_2 SUBJECT_SAMPLE_FACTORS - negMSMSALL-SC-D3-IR_SA127_1 Treatment:Non-IR Control Strain=C57BL/6J; RAW_FILE_NAME=negMSMSALL-SC-D3-IR_SA127_1 SUBJECT_SAMPLE_FACTORS - negMSMSALL-SC-D3-IR_SA127_2 Treatment:Non-IR Control Strain=C57BL/6J; RAW_FILE_NAME=negMSMSALL-SC-D3-IR_SA127_2 SUBJECT_SAMPLE_FACTORS - negMSMSALL-SC-D3-IR_SA152_1 Treatment:Non-IR + Scl-Ab Strain=C57BL/6J; RAW_FILE_NAME=negMSMSALL-SC-D3-IR_SA152_1 SUBJECT_SAMPLE_FACTORS - negMSMSALL-SC-D3-IR_SA152_2 Treatment:Non-IR + Scl-Ab Strain=C57BL/6J; RAW_FILE_NAME=negMSMSALL-SC-D3-IR_SA152_2 SUBJECT_SAMPLE_FACTORS - negMSMSALL-SC-D3-IR_SA153_1 Treatment:Non-IR + Scl-Ab Strain=C57BL/6J; RAW_FILE_NAME=negMSMSALL-SC-D3-IR_SA153_1 SUBJECT_SAMPLE_FACTORS - negMSMSALL-SC-D3-IR_SA153_2 Treatment:Non-IR + Scl-Ab Strain=C57BL/6J; RAW_FILE_NAME=negMSMSALL-SC-D3-IR_SA153_2 SUBJECT_SAMPLE_FACTORS - negMSMSALL-SC-D3-IR_SA158_1 Treatment:Non-IR + Scl-Ab Strain=C57BL/6J; RAW_FILE_NAME=negMSMSALL-SC-D3-IR_SA158_1 SUBJECT_SAMPLE_FACTORS - negMSMSALL-SC-D3-IR_SA158_2 Treatment:Non-IR + Scl-Ab Strain=C57BL/6J; RAW_FILE_NAME=negMSMSALL-SC-D3-IR_SA158_2 #COLLECTION CO:COLLECTION_SUMMARY Lipidomic analyses were performed on mouse serum (n=3) collected through CO:COLLECTION_SUMMARY submandibular and terminal blood collections. Blood samples were extracted (10% CO:COLLECTION_SUMMARY of total body weight) and allowed to clot for 60 minutes at room temperature at CO:COLLECTION_SUMMARY which point the samples were centrifuged for 15 minutes at 12,000 RCF. The upper CO:COLLECTION_SUMMARY phase containing serum was transferred to a new, sterile microcentrifuge tube CO:COLLECTION_SUMMARY and frozen at -80°C. CO:SAMPLE_TYPE Blood (serum) CO:COLLECTION_METHOD submandibular and terminal blood collection CO:COLLECTION_FREQUENCY Day 3 and Day 35 CO:STORAGE_CONDITIONS -80℃ CO:COLLECTION_VIALS sterile microcentrifuge tube CO:STORAGE_VIALS sterile microcentrifuge tube #TREATMENT TR:TREATMENT_SUMMARY Forty female C57BL/6J mice (Jackson Laboratory, Bar Harbor, ME, USA), 12 weeks TR:TREATMENT_SUMMARY of age, were randomly split between two cohorts; Irradiated (IR) and TR:TREATMENT_SUMMARY Non-Irradiated (Non-IR) (n=20) and were used for all experiments. Two sub-lethal TR:TREATMENT_SUMMARY doses of cesium-137 (Cs-137) whole-body irradiation (2x 3 Gy; total of 6 Gy) TR:TREATMENT_SUMMARY with an exposure time of 3.72 minutes per mouse (total of 7.44 minutes) were TR:TREATMENT_SUMMARY administered 4 hours apart to the IR mice (n=20) on Day 0. Within each cohort, TR:TREATMENT_SUMMARY mice were sub-divided into treatment groups; Vehicle and Scl-Ab VI (25 mg/kg) TR:TREATMENT_SUMMARY (supplied by Amgen Inc/UCB Pharma) (n=10/per treatment). All mice were TR:TREATMENT_SUMMARY administered either a sterile phosphate buffered saline (PBS) vehicle control or TR:TREATMENT_SUMMARY Scl-Ab (25 mg/kg), once weekly via subcutaneous injections for a duration of 5 TR:TREATMENT_SUMMARY weeks, starting on Day 0. No adverse effects were observed after the TR:TREATMENT_SUMMARY administration of Scl-Ab. All experimental studies and procedures involving mice TR:TREATMENT_SUMMARY were performed in accordance with protocols approved by the governing TR:TREATMENT_SUMMARY Institutional Animal Care and Use Committee (IACUC). Additional Study Design and TR:TREATMENT_SUMMARY Drug Treatment information can be found in the Supplemental Material. TR:TREATMENT Neutralizing antibodies to sclerostin (Scl-Ab) TR:TREATMENT_ROUTE subcutaneous injections TR:TREATMENT_DOSE 25 mg/kg TR:TREATMENT_DOSEDURATION once weekly for 5 weeks TR:TREATMENT_VEHICLE sterile phosphate buffered saline (PBS) vehicle control TR:TREATMENT_COMPOUND Scl-Ab VI (supplied by Amgen Inc/UCB Pharma) #SAMPLEPREP SP:SAMPLEPREP_SUMMARY Three 12 µL serum aliquots per treatment (representative of individual mice) SP:SAMPLEPREP_SUMMARY were provided to the MMCRI Proteomics and Lipidomics Core Facility for analysis. SP:SAMPLEPREP_SUMMARY The individual samples were sub-divided into technical replicates, which were SP:SAMPLEPREP_SUMMARY then averaged together. Lipid extracts were dissolved in SP:SAMPLEPREP_SUMMARY methanol/dichloromethane for mass spectrometry (MS) analysis. Lipidomic analyses SP:SAMPLEPREP_SUMMARY were completed via 5600 TripleTOF mass spectrometer (Sciex, Framingham, MA) and SP:SAMPLEPREP_SUMMARY downstream analyses, including t-tests and principal component analyses (PCAs), SP:SAMPLEPREP_SUMMARY were completed utilizing MarkerView Software (Sciex). PCAs were performed with SP:SAMPLEPREP_SUMMARY no weighting, Pareto scaling, and supervised data analysis. Lipids were analyzed SP:SAMPLEPREP_SUMMARY using a global, bias-free lipid profiling acquisition technique (MS/MSALL). SP:PROCESSING_STORAGE_CONDITIONS -80℃ SP:EXTRACT_STORAGE -80℃ #CHROMATOGRAPHY CH:CHROMATOGRAPHY_SUMMARY Direct infusion CH:CHROMATOGRAPHY_TYPE None (Direct infusion) CH:INSTRUMENT_NAME Sciex TripleTOF 5600 CH:COLUMN_NAME none #ANALYSIS AN:ANALYSIS_TYPE MS AN:LABORATORY_NAME Proteomics and Lipidomics Core AN:OPERATOR_NAME Calvin Vary #MS MS:INSTRUMENT_NAME ABI Sciex 5600 TripleTOF MS:INSTRUMENT_TYPE QTOF MS:MS_TYPE ESI MS:ION_MODE NEGATIVE MS:MS_COMMENTS Direct infusion positive and negative mode MSMSALL workflow Sciex-LipidView; MS:MS_COMMENTS Sciex-MarkerView MS:MS_RESULTS_FILE ST001704_AN002776_Results.txt UNITS:m/z Has m/z:No Has RT:No RT units:No RT data #END