Rattus norvegicus
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ABSTRACT:
PROVIDER: PRJNA290869 | ENA |
REPOSITORIES: ENA
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Project description: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. 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 4â6 ?m 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
2016-01-06 | E-GEOD-71306 | biostudies-arrayexpress
Project description: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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Project description:Acupuncture treatment is based on acupoint stimulation; however, the biological basis is not understood. We stimulated one acupoint with catgut embedding (CEP) for 8 weeks and then used isobaric tags for relative and absolute quantitation to screen proteins with altered expression in adjacent acupoints of Sprague Dawley rats. The expression levels of 10 proteins, including kininogen (KNG), consistently changed >1.5-fold in all three acupoints in CEP versus sham CEP-treated rats. Eight-week, but not 3-day, CEP treatment enhanced KNG expression. The enhanced KNG expression among small vessels in the subcutaneous layer was revealed via immunofluorescence. Nitric oxide synthesis was enhanced similar to KNG. These findings uncover biological changes at acupoints and suggest the critical role of the KNG–nitric oxide signaling pathway in acupoint activation.
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Project description: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.
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Project description:In this work we study the pulmonary toxicological properties of carbon nanotubes using molecular toxicological approache. For this, we exposed Sprague Dawley rats by nose-only inhalation 6 hours/day, 5 days/week for 4 weeks. Lung samples have been collected up to 180 days after the end of exposure and transcriptomics analysis were performed.
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