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

Abstract

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 themore » 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.« less

Authors:

Ross, Ryan D. ^[1]; Mashiatulla, Maleeha ^[2]; Acerbo, Alvin S. ^[3]; Almer, Jonathan D. ^[4]; Miller, Lisa ^[5]; Johnson, Mark L. ^[6]; Summer, D. Rick ^[2]

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+ Show Author Affiliations

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:

Thu May 26 00:00:00 EDT 2016

Research Org.:

Brookhaven National Laboratory (BNL), Upton, NY (United States); Argonne National Laboratory (ANL), Argonne, IL (United States)

Sponsoring Org.:

USDOE Office of Science (SC), Basic Energy Sciences (BES); 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