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| Status |
Public on Jan 06, 2016 |
| Title |
Scl-Ab: Exploratory 26-Week Subcutaneous Toxicology Study in the Aged Ovariectomized Female Sprague Dawley Rat with an 18-week Recovery [vertebrae] |
| Organism |
Rattus norvegicus |
| Experiment type |
Expression profiling by array
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| Summary |
This study is designed to compare and contrast the temporal and spatial changes in bone formation rates and transcriptional profiles in cortical and cancellous bone cell populations enriched by laser capture microdissection (LCM) in ovariectomized rats administered Scl-Ab by subcutaneous injection for up to 26 consecutive weeks, followed by a recovery period of up to 18 weeks.
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| Overall design |
Six-month-old Sprague-Dawley female rats were OVX, left untreated for 8 weeks. Rats were assigned to three treatment groups using a computerized blocking procedure designed to achieve body weight balance across treatment groups and then divided into three groups and administered by s.c. injection VEH or 3 or 50 mg/kg/wk of a Scl-Ab engineered to be less immunogenic in rats up to d183. Rats were administered either VEH or 3 or 50 mg/kg of Scl-Ab once weekly by s.c. injection. Up to 15 rats per group were euthanized at d8, 29, 85, and 183. To assess effects following treatment withdrawal, additional groups were maintained through a treatment-free period (TFP) and euthanized at d197 and 267 for VEH and 3 mg/kg groups and at d237 and 309 for VEH and 50 mg/kg groups. To label active bone-forming surfaces and facilitate osteoblast (OB) and lining cell (LC) enrichment during laser capture microdissection (LCM), 10 mg/kg calcein green was administered s.c. 13 and 3 days prior to scheduled euthanasia. At necropsy, the first and second lumbar vertebral (L1 and L2) bodies were isolated for histomorphometry and pQCT analyses, respectively. Cryosection preparation of L3 vertebral body, LCM procedure and validation of cell enrichment, RNA extraction and amplification, TaqMan, and initial microarray analysis was performed. LCM was performed on 4-6 µm cryosections of vertebrae from the first 5 animals per treatment group per timepoint to enrich for OB, LC, and osteocyte (OCy) subpopulations for transcriptional analyses using Affmetrix Rat 230_2 microarrays
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| Contributor(s) |
Taylor S, Ominsky MS, Hu R, Pacheco E, He YD, Buntich S, Afshari CA, Pyrah I, Nioi P, Boyce RW |
| Citation(s) |
26721737 |
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| Submission date |
Jul 24, 2015 |
| Last update date |
Jul 31, 2017 |
| Contact name |
Scott Taylor |
| E-mail(s) |
Scott.Taylor@Amgen.com
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| Organization name |
Amgen Inc.
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| Street address |
One Amgen Center Drive
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| City |
Thousand Oaks |
| State/province |
CA |
| ZIP/Postal code |
91320-1799 |
| Country |
USA |
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| Platforms (1) |
| GPL1355 |
[Rat230_2] Affymetrix Rat Genome 230 2.0 Array |
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| Samples (294)
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| Relations |
| BioProject |
PRJNA290869 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE71306_RAW.tar |
608.9 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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