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Publication
Low bone toughness in the TallyHO model of juvenile type 2 diabetes does not
worsen with age.
Authors Creecy A, Uppuganti S, Unal M, Clay Bunn R, Voziyan P, Nyman JS
Submitted By Submitted Externally on 3/23/2018
Status Published
Journal Bone
Year 2018
Date Published 2/1/2018
Volume : Pages 110 : 204 - 214
PubMed Reference 29438824
Abstract Fracture risk increases as type 2 diabetes (T2D) progresses. With the rising
incidence of T2D, in particular early-onset T2D, a representative pre-clinical
model is needed to study mechanisms for treating or preventing diabetic bone
disease. Towards that goal, we hypothesized that fracture resistance of bone
from diabetic TallyHO mice decreases as the duration of diabetes increases.
Femurs and lumbar vertebrae were harvested from male, TallyHO mice and male,
non-diabetic SWR/J mice at 16weeks (n=12 per strain) and 34weeks (n=13 per
strain) of age. As is characteristic of this model of juvenile T2D, the TallyHO
mice were obese and hyperglycemic at an early age (5weeks and 10weeks of age,
respectively). The femur mid-shaft of TallyHO mice had higher tissue mineral
density and larger cortical area, as determined by micro-computed tomography,
compared to the femur mid-shaft of SWR/J mice, irrespective of age. As such, the
diabetic rodent bone was structurally stronger than the non-diabetic rodent
bone, but the higher peak force endured by the diaphysis during three-point
(3pt) bending was not independent of the difference in body weight. Upon
accounting for the structure of the femur diaphysis, the estimated toughness at
16weeks and 34weeks was lower for the diabetic mice than for non-diabetic
controls, but neither toughness nor estimated material strength and resistance
to crack growth (3pt bending of contralateral notched femur) decreased as the
duration of hyperglycemia increased. With respect to trabecular bone, there were
no differences in the compressive strength of the L6 vertebral strength between
diabetic and non-diabetic mice at both ages despite a lower trabecular bone
volume for the TallyHO than for the SWR/J mice at 34weeks. Amide I sub-peak
ratios as determined by Raman Spectroscopy analysis of the femur diaphysis
suggested a difference in collagen structure between diabetic and non-diabetic
mice, although there was not a significant difference in matrix pentosidine
between the groups. Overall, the fracture resistance of bone in the TallyHO
model of T2D did not progressively decrease with increasing duration of
hyperglycemia. However, given the variability in hyperglycemia in this model,
there were correlations between blood glucose levels and certain structural
properties including peak force.




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