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

Abstract

Here, the G171V mutation in the low density lipoprotein receptor-related protein 5 (LRP5) leads to a high bone mass (HBM) phenotype. Studies using an HBM transgenic mouse model have consistently found increased bone mass and whole-bone strength, but little attention has been paid to bone matrix quality. 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. Interestingly, 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 and carbonate substitution, but no differences in crystal length, intra-fibular strains, and mineral spacing compared to wild-type controls. The largest difference in material properties was a 2-fold increase in the modulus of toughness in HBM mice. Step-wise regression analyses found weak correlations between matrix composition and material properties, and interestingly, the matrix compositional parameters associated with themore » 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 greater bone quantity, but also to improve bone quality.« less

Authors:
 [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)
Publication Date:
Research Org.:
Brookhaven National Lab. (BNL), Upton, NY (United States); Argonne National Lab. (ANL), Argonne, IL (United States)
Sponsoring Org.:
USDOE Office of Science (SC), Basic Energy Sciences (BES) (SC-22); National Institutes of Health (NIH)
OSTI Identifier:
1340417
Alternate Identifier(s):
OSTI ID: 1389621
Report Number(s):
BNL-113304-2016-JA
Journal ID: ISSN 0171-967X
Grant/Contract Number:  
SC00112704; AC02-06CH11357
Resource Type:
Accepted Manuscript
Journal Name:
Calcified Tissue International
Additional Journal Information:
Journal Volume: 99; Journal Issue: 4; Journal ID: ISSN 0171-967X
Publisher:
Springer
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; HBM; LRP5; Matrix Composition; Mineralization; Collagen Cross-linking; Toughness

Citation Formats

Ross, Ryan D., Mashiatulla, Maleeha, Acerbo, Alvin S., Almer, Jonathan D., Miller, Lisa, Johnson, Mark L., and Summer, D. Rick. HBM Mice Have Altered Bone Matrix Composition And Improved Material Toughness. United States: N. p., 2016. Web. doi:10.1007/s00223-016-0154-2.
Ross, Ryan D., Mashiatulla, Maleeha, Acerbo, Alvin S., Almer, Jonathan D., Miller, Lisa, Johnson, Mark L., & Summer, D. Rick. HBM Mice Have Altered Bone Matrix Composition And Improved Material Toughness. United States. doi:10.1007/s00223-016-0154-2.
Ross, Ryan D., Mashiatulla, Maleeha, Acerbo, Alvin S., Almer, Jonathan D., Miller, Lisa, Johnson, Mark L., and Summer, D. Rick. Thu . "HBM Mice Have Altered Bone Matrix Composition And Improved Material Toughness". United States. doi:10.1007/s00223-016-0154-2. https://www.osti.gov/servlets/purl/1340417.
@article{osti_1340417,
title = {HBM Mice Have Altered Bone Matrix Composition And Improved Material Toughness},
author = {Ross, Ryan D. and Mashiatulla, Maleeha and Acerbo, Alvin S. and Almer, Jonathan D. and Miller, Lisa and Johnson, Mark L. and Summer, D. Rick},
abstractNote = {Here, the G171V mutation in the low density lipoprotein receptor-related protein 5 (LRP5) leads to a high bone mass (HBM) phenotype. Studies using an HBM transgenic mouse model have consistently found increased bone mass and whole-bone strength, but little attention has been paid to bone matrix quality. 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. Interestingly, 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 and carbonate substitution, but no differences in crystal length, intra-fibular strains, and mineral spacing compared to wild-type controls. The largest difference in material properties was a 2-fold increase in the modulus of toughness in HBM mice. Step-wise regression analyses found weak correlations between matrix composition and material properties, and interestingly, the matrix compositional parameters associated with the 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 greater bone quantity, but also to improve bone quality.},
doi = {10.1007/s00223-016-0154-2},
journal = {Calcified Tissue International},
number = 4,
volume = 99,
place = {United States},
year = {2016},
month = {5}
}

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