How tough Is brittle bone? Investigating osteogenesis imperfecta in mouse bone
File(s)nihms-694239.pdf (1.17 MB)
Accepted version
Author(s)
Type
Journal Article
Abstract
The multiscale hierarchical structure of bone is naturally optimized to resist fractures. In osteogenesis imperfecta, or brittle bone disease, genetic mutations affect the quality and/or quantity of collagen, dramatically increasing bone fracture risk. Here we reveal how the collagen defect results in bone fragility in a mouse model of osteogenesis imperfecta (oim), which has homotrimeric α1(I) collagen. At the molecular level, we attribute the loss in toughness to a decrease in the stabilizing enzymatic cross-links and an increase in nonenzymatic cross-links, which may break prematurely, inhibiting plasticity. At the tissue level, high vascular canal density reduces the stable crack growth, and extensive woven bone limits the crack-deflection toughening during crack growth. This demonstrates how modifications at the bone molecular level have ramifications at larger length scales affecting the overall mechanical integrity of the bone; thus, treatment strategies have to address multiscale properties in order to regain bone toughness. In this regard, findings from the heterozygous oim bone, where defective as well as normal collagen are present, suggest that increasing the quantity of healthy collagen in these bones helps to recover toughness at the multiple length scales.
Date Issued
2014-06-01
Online Publication Date
2014-01-13
2015-06-26T15:31:51Z
Date Acceptance
2014-01-09
ISSN
0884-0431
Publisher
Wiley
Start Page
1392
End Page
1401
Journal / Book Title
Journal of Bone and Mineral Research
Volume
29
Issue
6
Copyright Statement
This is the peer reviewed version of the following article: Carriero, A., Zimmermann, E. A., Paluszny, A., Tang, S. Y., Bale, H., Busse, B., Alliston, T., Kazakia, G., Ritchie, R. O. and Shefelbine, S. J. (2014), How Tough Is Brittle Bone? Investigating Osteogenesis Imperfecta in Mouse Bone. J Bone Miner Res, 29: 1392–1401, which has been published in final form at https://dx.doi.org/10.1002/jbmr.2172. This article may be used for non-commercial purposes in accordance With Wiley Terms and Conditions for self-archiving.
Source Database
web-of-science
Identifier
https://asbmr.onlinelibrary.wiley.com/doi/full/10.1002/jbmr.2172
Subjects
Science & Technology
Life Sciences & Biomedicine
Endocrinology & Metabolism
ENDOCRINOLOGY & METABOLISM
BRITTLE BONE
BONE FRACTURE
FRACTURE MECHANICS
MOUSE BONE
CRACK INITIATION
CRACK GROWTH
FATIGUE-CRACK-PROPAGATION
HUMAN CORTICAL BONE
AGE-RELATED-CHANGES
OIM MICE EXHIBIT
COMPACT-BONE
MINERAL CONTENT
MURINE MODEL
COLLAGEN
MUTATION
FRACTURE
Science & Technology
Life Sciences & Biomedicine
Endocrinology & Metabolism
BRITTLE BONE
BONE FRACTURE
FRACTURE MECHANICS
MOUSE BONE
CRACK INITIATION
CRACK GROWTH
FATIGUE-CRACK-PROPAGATION
HUMAN CORTICAL BONE
AGE-RELATED-CHANGES
OIM MICE EXHIBIT
COMPACT-BONE
MINERAL CONTENT
MURINE MODEL
COLLAGEN
MUTATION
FRACTURE
BONE FRACTURE
BRITTLE BONE
CRACK GROWTH
CRACK INITIATION
FRACTURE MECHANICS
MOUSE BONE
Animals
Biomechanical Phenomena
Bone Density
Bone and Bones
Computer Simulation
Fibrillar Collagens
Fractures, Bone
Glycation End Products, Advanced
Mice
Mice, Inbred C57BL
Osteogenesis Imperfecta
Scattering, Small Angle
Spectroscopy, Fourier Transform Infrared
Tomography, X-Ray Computed
X-Ray Diffraction
Bone and Bones
Animals
Mice, Inbred C57BL
Mice
Osteogenesis Imperfecta
Fibrillar Collagens
Tomography, X-Ray Computed
X-Ray Diffraction
Spectroscopy, Fourier Transform Infrared
Bone Density
Computer Simulation
Fractures, Bone
Scattering, Small Angle
Biomechanical Phenomena
Glycation End Products, Advanced
Anatomy & Morphology
06 Biological Sciences
09 Engineering
11 Medical and Health Sciences
Publication Status
Published
Date Publish Online
2014-01-13