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Title: HBM Mice Have Altered Bone Matrix Composition And Improved Material Toughness

Journal Article · · Calcified Tissue International
 [1];  [2];  [3];  [4];  [5];  [6];  [2]
  1. Rush Univ. Medical Center, Chicago, IL (United States)
  2. Rush Univ. Medical Center, Chicago, IL (United States); Univ. of Illinois, Chicago, IL (United States)
  3. Univ. of Chicago, IL (United States). Center for Advanced Radiation Sources (CARS); Brookhaven National Lab. (BNL), Upton, NY (United States)
  4. Argonne National Lab. (ANL), Argonne, IL (United States)
  5. Brookhaven National Lab. (BNL), Upton, NY (United States). National Synchrotron Light Source
  6. Univ. of Missouri, Kansas City, MO (United States)
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The G171V mutation in the low-density lipoprotein receptor-related protein 5 (LRP5) leads to a high bone mass (HBM) phenotype. Studies using HBM transgenic mouse models have consistently found increased bone mass and whole-bone strength, but little attention has been paid to the composition of the bone matrix. The current study sought to determine if the cortical bone matrix composition differs in HBM and wild-type mice and to determine how much of the variance in bone material properties is explained by variance in matrix composition. Consistent with previous studies, HBM mice had greater cortical area, moment of inertia, ultimate force, bending stiffness, and energy to failure than wild-type animals. The increased energy to failure was primarily caused by a large increase in post-yield behavior, with no difference in pre-yield behavior. The HBM mice had increased mineral-to-matrix and collagen cross-link ratios, and decreased crystallinity, carbonate, and acid phosphate substitution as measured by Fourier transform infrared microspectroscopy, but no differences in crystal length, intra-fibular strains, and mineral spacing compared to wild-type controls, as measured by X-ray scattering. The largest between genotype difference in material properties was a twofold increase in the modulus of toughness in HBM mice. Step-wise regression analyses showed that the specific matrix compositional parameters most closely associated with material properties varied between the wild-type and HBM genotypes. Although the mechanisms controlling the paradoxical combination of more mineralized yet tougher bone in HBM mice remain to be fully explained, the findings suggest that LRP5 represents a target to not only build bone mass but also to improve bone quality.

Research Organization:
Brookhaven National Laboratory (BNL), Upton, NY (United States); Argonne National Laboratory (ANL), Argonne, IL (United States)
Sponsoring Organization:
USDOE Office of Science (SC), Basic Energy Sciences (BES); National Institutes of Health (NIH)
Grant/Contract Number:
SC00112704; AC02-06CH11357
OSTI ID:
1340417
Alternate ID(s):
OSTI ID: 1389621
Report Number(s):
BNL-113304-2016-JA
Journal Information:
Calcified Tissue International, Vol. 99, Issue 4; ISSN 0171-967X
Publisher:
SpringerCopyright Statement
Country of Publication:
United States
Language:
English
Citation Metrics:
Cited by: 6 works
Citation information provided by
Web of Science

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Related Subjects

59 BASIC BIOLOGICAL SCIENCES
HBM
LRP5
Matrix Composition
Mineralization
Collagen Cross-linking
Toughness