Repeated irradiation from micro-computed tomography scanning at 2, 4 and 6 months of age does not induce damage to tibial bone microstructure in male and female CD-1 mice
: Long-term effects of repeated in vivo micro-computed tomography (μCT) scanning at key stages of growth and bone development (ages 2, 4 and 6 months) on trabecular and cortical bone structure, as well as developmental patterns, have not been studied. We determined the effect of repetitive μCT scanning at age 2, 4 and 6 months on tibia bone structure of male and female CD-1 mice and characterized developmental changes. At 2, 4 and 6 months of age, right tibias were scanned using in vivo μCT (Skyscan 1176) at one of three doses of radiation per scan: 222, 261 or 460 mGy. Left tibias of the same mice were scanned only at 6 months to serve as non-irradiated controls to determine whether recurrent radiation exposure alters trabecular and cortical bone structure at the proximal tibia. In males, eccentricity was lower (P<0.05) in irradiated compared with non-irradiated tibias (222 mGy group). Within each sex, all other structural outcomes were similar between irradiated and non-irradiated tibias regardless of dose. Trabecular bone loss occurred in all mice due to age while cortical development continued to age 6 months. In conclusion, repetitive μCT scans at various radiation doses did not damage trabecular or cortical bone structure of proximal tibia in male and female CD-1 mice. Moreover, scanning at 2, 4 and 6 months of age highlight the different developmental time course between trabecular and cortical bone. These scanning protocols can be used to investigate longitudinal responses of bone structures to an intervention.
In vivo micro-computed tomography (μCT) provides the ability to measure longitudinal changes to tibia microarchitecture, but the effect of this radiation is not well understood. The right proximal tibia of Sprague–Dawley rats (n = 12/group) randomized to Sham-control (Sham) or ovariectomy (OVX) surgery at 12 weeks of age was scanned using μCT at 13, 17, 21, and 25 weeks of age, at a resolution of 18 μm and a radiation dose of 603 mGy. The left proximal tibia was scanned only at 25 weeks of age t...
Physical activity is essential to maintain skeletal mass and structure, but its effect seems to diminish with age. To test the hypothesis that bone becomes less sensitive to mechanical strain with age, we used a combined in vivo/in silico approach. We investigated how maturation and aging influence the mechanical regulation of bone formation and resorption to 2 weeks of noninvasive in vivo controlled loading in mice. Using 3D in vivo morphometrical assessment of longitudinal microcomputed tomogr...
#2Wendy E. Ward(U of T: University of Toronto)H-Index: 32
Abstract Female mice exposed to soy isoflavones (ISO) during early postnatal life have improved bone outcomes at adulthood. Since long-lasting effects may be mediated by DNA methylation, we hypothesized that providing supplemental folic acid (FA), a methyl donor, during early life, would enhance the positive effect of ISO to bone health. Bone-specific gene expression patterns were studied to understand potential mechanisms. CD-1 dams ( n =36) were randomized to adequate or supplemental levels of...
Last. Brigitte Demes(SBU: Stony Brook University)H-Index: 32
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Abstract Effects of load-bearing exercise on skeletal structure and mechanical properties can vary between inbred strains of mice. Here, we examine whether such variation also exists at the population level. An experiment was performed with two outbred mouse stocks that have been reproductively isolated for > 120 generations (Hsd:ICR, Crl:CD1). Growing females from each stock were either treated with a treadmill-running regimen for 1 month or served as controls. Limb forces were recorded with a ...
Abstract Periostin (a product of Postn gene) is a matricellular protein which is increased in periosteal osteoblasts and osteocytes upon mechanical stimulation. We previously reported that periostin-deficient mice ( Postn −/− ) have low bone mass and a diminished response to physical activity due to a lack of sclerostin (a product of Sost gene) inhibition by mechanical loading. Here we hypothesized that periostin could play a central role in the control of bone loss during unloading induced by h...
#1Abdul Malik Tyagi(CSIR: Council of Scientific and Industrial Research)H-Index: 21
#2Mohd Nizam Mansoori(CSIR: Council of Scientific and Industrial Research)H-Index: 9
Last. Divya Singh(CSIR: Council of Scientific and Industrial Research)H-Index: 25
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Activated T cell has a key role in the interaction between bone and immune system. T cells produce proinflammatory cytokines, including receptor activator of NF-κB ligand (RANKL), tumor necrosis factor α (TNF-α), and interleukin 17 (IL-17), all of which augment osteoclastogenesis. RANKL and TNF-α are targeted by inhibitors such as denosumab, a human monoclonal RANKL antibody, and infliximab, which neutralizes TNF-α. IL-17 is also an important mediator of bone loss, and an antibody against IL-17 ...
Micro-computed tomography (micro-CT) is a high-resolution imaging modality that is capable of analysing bone structure with a voxel size on the order of 10 μm. With the development of in vivo micro-CT, where disease progression and treatment can be monitored in a living animal over a period of time, this modality has become a standard tool for preclinical assessment of bone architecture during disease progression and treatment. For meaningful comparison between micro-CT studies, it is essential ...
Last. Claes Ohlsson(University of Gothenburg)H-Index: 116
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The bone-sparing effect of estrogen is primarily mediated via estrogen receptor (ER) α, which stimulates target gene transcription through two activation functions (AFs), AF-1 in the N-terminal and AF-2 in the ligand-binding domain. It was recently demonstrated that the ER antagonist ICI 182,780 (ICI) acts as an ER agonist in uterus of mice with mutations in the ERα AF-2. To evaluate the estrogen-like effects of ICI in different tissues, ovariectomized wild-type mice and mice with mutations in t...
Abstract Trabecular bone is a highly dynamic tissue due to bone remodeling, mineralization and demineralization. The mineral content and its spatial heterogeneity are main contributors to bone quality. Using time-lapsed in vivo micro-computed tomography (micro-CT), it is now possible to resolve in three dimensions where bone gets resorbed and deposited over several weeks. In addition, the gray values in the micro-CT images contain quantitative information about the local tissue mineral density (...
Last. Geert Carmeliet(Katholieke Universiteit Leuven)H-Index: 68
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Abstract In vivo micro-computed tomography (micro-CT) will offer unique information on the time-related changes in bone mass and structure of living mice, provided that radiation-induced side effects are prevented. Lowering the radiation dose, however, inevitably decreases the image quality. In this study we developed and validated a protocol for in vivo micro-CT imaging of mouse bone architecture that retains high quality images but avoids radiation-induced side effects on bone structure and he...
Chronic low-grade inflammation has been identified as an underlying cause of many diseases including osteoporosis. Lipopolysaccharide (LPS) is a potent inducer of the inflammatory response that can negatively affect bone outcomes by upregulating bone resorption and inhibiting bone formation. The objective of this study was to assess the longitudinal response of trabecular and cortical bone structure and bone mineral density to LPS continuously administered for 12 weeks in male and female CD-1 mi...
Abstract While repeated in vivo micro-computed tomography (μCT) allows for longitudinal measurement of bone outcomes in rodent models, it is important to determine that the resulting irradiation – dependent on the frequency and number of scans - does not exceed the effects of the intervention. The objective of this study was to determine whether repeated irradiation exposure from μCT scans at 1-month intervals for a total of four scans would alter trabecular or cortical bone structure outcomes a...
#1Emma C Walker(St. Vincent's Institute of Medical Research)H-Index: 13
#2Kim Truong(St. Vincent's Institute of Medical Research)H-Index: 1
Last. Natalie A. Sims(St. Vincent's Institute of Medical Research)H-Index: 67
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Bone strength is determined by its dense cortical shell, generated by unknown mechanisms. Here we use the Dmp1Cre:Socs3f/f mouse, with delayed cortical bone consolidation, to characterise cortical maturation and identify control signals. We show that cortical maturation requires a reduction in cortical porosity, and a transition from low to high density bone, which continues even after cortical shape is established. Both processes were delayed in Dmp1Cre:Socs3f/f mice. SOCS3 (suppressor of cytok...
Last. Dawei Yao(NAU: Nanjing Agricultural University)H-Index: 1
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Abstract Thirty six 56-week-old ISA cage layers were divided into two groups randomly. The cage layers in control group (12 birds) and experiment group (24 birds) were respectively injected with 300 µL sodium chloride and 300 μg eucaryon recombinant plasmid pcDNA3.1(+)-chOPG. Eighty 56-week-old ISA cage layers were divided into group A, B, C and D randomly. Group A is for control group, while plasmid pcDNA3.1(+)-chOPG was injected to B, C, D groups in muscle at the dosage of 200 μg, 400 μg, 600 ...
In longitudinal studies, in vivo micro-Computed Tomography (microCT) imaging is used to investigate bone changes over time due to interventions in mice. However, ionising radiation can provoke significant variations in bone morphometric parameters. In a previous study, we evaluated the effect of reducing the integration time on the properties of the mouse tibia measured from microCT images. A scanning procedure (100 ms integration time, 256 mGy nominal radiation dose) was selected as the best co...
Last. Wendy E. Ward(U of T: University of Toronto)H-Index: 32
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Abstract Background Calcium (Ca) and vitamin D (vit D) in the AIN-93G diet may be higher than required for healthy bone development, and mask the potential benefit of a dietary intervention. Objective The objective was to determine if lower levels of Ca and vit D than is present in the AIN-93G diet supports bone development in growing male CD-1 mice. Methods Weanling male CD-1 mice were randomized to modified AIN-93G diets containing either 100 (Trial 1) or 400 (Trial 2) IU vit D/kg diet within ...
Ionizing radiation constitutes a health risk to imaging scientists and study animals. Both PET and CT produce ionizing radiation. CT doses in pre-clinical in vivo imaging typically range from 50 to 1,000 mGy and biological effects in mice at this dose range have been previously described. [ 18 F]FDG body doses in mice have been estimated to be in the range of 100 mGy for [ 18 F]FDG. Yearly, the average whole body doses due to handling of activity by PET technologists are reported to be 3-8 mSv. ...
This Horizons is part of a series that identifies key, forward-thinking research questions and challenges that need to be addressed. Specifically, this Horizons paper discusses research in nutritio...
AbstractBone is a mechanically active, three-dimensionally (3D) complex, and dynamic tissue that changes in structure over the human lifespan. Bone tissue exists and remodels in 3D and changes over time, introducing a fourth dimension. The products of the remodelling process, secondary and fragmentary osteons, have been studied substantially using traditional two-dimensional (2D) techniques. As a result, much has been learned regarding the biological information encrypted in the histomorphology ...