Browsing by Subject "Fracture toughness"

Now showing 1 - 5 of 5
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    Limited Impacts of Thermoneutral Housing on Bone Morphology and Mechanical Properties in Growing Female Mice Exposed to External Loading and Raloxifene Treatment
    (Elsevier, 2021) Tastad, Carli A.; Kohler, Rachel; Wallace, Joseph M.; Biomedical Engineering, School of Engineering and Technology
    Thermoregulation is an important factor that could have physiological consequences on pre-clinical research outcomes. Simply housing mice at thermoneutral temperature has been shown to prevent the well-established loss of cancellous bone that is typical in growing mice. In this study, active tissue formation was induced by non-invasive tibial loading in female mice and combined with raloxifene treatment to assess whether temperature could enhance their combined effects on bone morphology and mechanical properties. It was hypothesized that by removing the cold stress under which normal lab mice are housed, a metabolic boost would allow for further architectural and mechanical improvements in mice exposed to a combination of tibial loading and raloxifene. Ten-week old female C57BL/6J mice were treated with raloxifene, underwent tibial loading to a maximum tensile stress of 2050 με, and were housed in thermoneutral conditions (32 °C) for 6 weeks. We investigated bone morphology through microcomputed tomography (μCT), mechanical properties via four-point bending, and fracture toughness testing. Results confirmed previous work showing a combined effect of external loading and raloxifene which led to greater improvements in most properties than either individual treatment. Counter to the hypothesis, temperature had modest effects on body weight, overall bone size, and trabecular architecture, and most effects were detrimental. Thermoneutrality had no impact on mechanical integrity or fracture toughness. In most cases, the magnitude of temperature-based effects were less robust than either RAL treatment or loading.
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    Metabolic and Skeletal Characterization of the KK/Ay Mouse Model – a Polygenic Mutation Model of Obese Type 2 Diabetes
    (Springer, 2024) Chowdhury, Nusaiba N.; Surowiec, Rachel K.; Kohler, Rachel K.; Reul, Olivia N.; Segvich, Dyann M.; Wallace, Joseph M.; Radiology and Imaging Sciences, School of Medicine
    Type 2 diabetes (T2D) increases fracture incidence and fracture-related mortality rates (KK.Cg-Ay/J. The Jackson Laboratory; Available from: https://www.jax.org/strain/002468 ). While numerous mouse models for T2D exist, few effectively stimulate persistent hyperglycemia in both sexes, and even fewer are suitable for bone studies. Commonly used models like db/db and ob/ob have altered leptin pathways, confounding bone-related findings since leptin regulates bone properties (Fajardo et al. in Journal of Bone and Mineral Research 29(5): 1025-1040, 2014). The Yellow Kuo Kondo (KK/Ay) mouse, a polygenic mutation model of T2D, is able to produce a consistent diabetic state in both sexes and addresses the lack of a suitable model of T2D for bone studies. The diabetic state of KK/Ay stems from a mutation in the agouti gene, responsible for coat color in mice. This mutation induces ectopic gene expression across various tissue types, resulting in diabetic mice with yellow fur coats (Moussa and Claycombe in Obesity Research 7(5): 506-514, 1999). Male and female KK/Ay mice exhibited persistent hyperglycemia, defining them as diabetic with blood glucose (BG) levels consistently exceeding 300 mg/dL. Notably, male control mice in this study were also diabetic, presenting a significant limitation. Nevertheless, male and female KK/Ay mice showed significantly elevated BG levels, HbA1c, and serum insulin concentration when compared to the non-diabetic female control mice. Early stages of T2D are characterized by hyperglycemia and hyperinsulinemia resulting from cellular insulin resistance, whereas later stages may feature hypoinsulinemia due to β-cell apoptosis (Banday et al. Avicenna Journal of Medicine 10(04): 174-188, 2020 and Klein et al. Cell Metabolism 34(1): 11-20, 2022). The observed hyperglycemia, hyperinsulinemia, and the absence of differences in β-cell mass suggest that KK/Ay mice in this study are modeling the earlier stages of T2D. While compromised bone microarchitecture was observed in this study, older KK/Ay mice, representing more advanced stages of T2D, might exhibit more pronounced skeletal manifestations. Compared to the control group, the femora of KK/Ay mice had higher cortical area and cortical thickness, and improved trabecular properties which would typically be indicative of greater bone strength. However, KK/Ay mice displayed lower cortical tissue mineral density in both sexes and increased cortical porosity in females. Fracture instability toughness of the femora was lower in KK/Ay mice overall compared to controls. These findings indicate that decreased mechanical integrity noted in the femora of KK/Ay mice was likely due to overall bone quality being compromised.
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    Physio-Mechanical Properties of a New Zinc-Reinforced Glass Ionomer Restorative Material
    (Office of the Vice Chancellor for Research, 2013-04-05) Al-Angari, Sarah; Hara, Anderson T.; Chu, Tien-Min Gabriel; Platt, Jeffrey A.; Eckert, George; Cook, Norman
    Objective: Zinc-reinforced glass ionomer restorative material (ZRGIC) has been proposed as an improved restorative material. The study compared the mechanical properties of a ZRGIC restorative material (ChemFil Rock, (Dentsply)), with three commercially available glass ionomers (GICs); Fuji IX GP Extra (GC America), Ketac Molar (3M ESPE) and EQUIA Fil (GC America). A resin composite, Premise (Kerr), was included as a control group. Methods: Fracture toughness (KIC) testing was done according to ISO 13586, using single edge notchedbeam specimens (n=10), loaded until failure in a three-point bending test device. Specimens (n=9) for the hardness, roughness and abrasive wear testing were made by mixing and inserting the restorative materials into individual stainless steel molds followed by flattening and polishing. Knoop microhardness (KHN) was performed (25g, 30s),on pre-determined areas of the polished surfaces. For toothbrushing wear resistance and roughness, specimens were brushed in an automated brushing machine (200g) with a suspension of dentifrice and water (1:1w/v) for 20,000 strokes. Specimen surfaces were scanned in an optical profilometer before and after brushing to obtain surface roughness (Ra) and mean height (surface) loss using image subtraction and dedicated software. Data were analyzed using Wilcoxon Rank Sum tests (α=0.05).
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    Removing or truncating connexin 43 in murine osteocytes alters cortical geometry, nanoscale morphology, and tissue mechanics in the tibia
    (Elsevier, 2016-07) Hammond, Max A.; Berman, Alycia G.; Pacheco-Costa, Rafael; Davis, Hannah M.; Plotkin, Lilian I.; Wallace, Joseph M.; Biomedical Engineering, School of Engineering and Technology
    Gap junctions are formed from ubiquitously expressed proteins called connexins that allow the transfer of small signaling molecules between adjacent cells. Gap junctions are especially important for signaling between osteocytes and other bone cell types. The most abundant type of connexin in bone is connexin 43 (Cx43). The C-terminal domain of Cx43 is thought to be an important modulator of gap junction function but the role that this domain plays in regulating tissue-level mechanics is largely unknown. We hypothesized that the lack of the C-terminal domain of Cx43 would cause morphological and compositional changes as well as differences in how bone responds to reference point indentation (RPI) and fracture toughness testing. The effects of the C-terminal domain of Cx43 in osteocytes and other cell types were assessed in a murine model (C57BL/6 background). Mice with endogenous Cx43 in their osteocytes removed via a Cre-loxP system were crossed with knock-in mice which expressed Cx43 that lacked the C-terminal domain in all cell types due to the insertion of a truncated allele to produce the four groups used in the study. The main effect of removing the C-terminal domain from osteocytic Cx43 increased cortical mineral crystallinity (p=0.036) and decreased fracture toughness (p=0.017). The main effect of the presence of the C-terminal domain in other cell types increased trabecular thickness (p<0.001), cortical thickness (p=0.008), and average RPI unloading slope (p=0.004). Collagen morphology was altered when either osteocytes lacked Cx43 (p=0.008) or some truncated Cx43 was expressed in all cell types (p<0.001) compared to controls but not when only the truncated form of Cx43 was expressed in osteocytes (p=0.641). In conclusion, the presence of the C-terminal domain of Cx43 in osteocytes and other cell types is important to maintain normal structure and mechanical integrity of bone.
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    Zoledronate and Raloxifene combination therapy enhances material and mechanical properties of diseased mouse bone
    (Elsevier, 2019-10-01) Powell, Katherine M.; Skaggs, Cayla; Pulliam, Alexis; Berman, Alycia; Allen, Matthew R.; Wallace, Joseph M.; Biomedical Engineering, School of Engineering and Technology
    Current interventions to reduce skeletal fragility are insufficient at enhancing both the quantity and quality of bone when attempting to improve overall mechanical integrity. Bisphosphonates, such as Zoledronate (ZOL), are used to treat a variety of bone disorders by increasing bone mass to decrease fracture risk, but long-term use has been shown in some settings to compromise bone quality. Alternatively, Raloxifene (RAL) has recently been demonstrated to improve tissue quality and overall mechanical properties in a cell-independent manner by binding to collagen and increasing tissue hydration. We hypothesized that a combination of RAL and ZOL would improve mechanical and material properties of bone more than either monotherapy alone by enhancing both quantity and quality. In this study, wildtype (WT) and heterozygous (OIM+/−) male mice from the Osteogenesis Imperfecta (OI) murine model were treated with either RAL, ZOL, or both from 8 weeks to 16 weeks of age. Using the OIM model allows for investigation of therapeutic effects on a quality-based bone disease. Combination treatment resulted in higher trabecular architecture, cortical mechanical properties, and cortical fracture toughness in diseased mouse bone. Two fracture toughness properties, which are direct measures of the tissue's ability to resist the initiation and propagation of a crack, were significantly improved with combination treatment in OIM+/− compared to control. There was no significant effect on fracture toughness with either monotherapy alone in either genotype. Following the mass-based effects of ZOL, trabecular bone volume fraction was significantly higher with combination treatment in both genotypes. Combination treatment resulted in higher ultimate stress in both genotypes. RAL and combination treatment in OIM+/− also increased resilience compared to the control. In conclusion, this study demonstrates the beneficial effects of using combination drug treatments to increase bone mass while simultaneously improving tissue quality, especially to enhance the mechanical integrity of diseased bone. Combination therapies could be a potential method to improve bone health and combat skeletal fragility on both the microscopic and macroscopic levels.