Significant deterioration in nanomechanical quality occurs through incomplete extrafibrillar mineralization in rachitic bone: Evidence from in-situ synchrotron X-ray scattering and backscattered electron imaging

Karunaratne, A., Esapa, C. R., Hiller, J., Boyde, A., Head, R., Bassett, J. H. D., Terrill, N. J., Williams, G. R., Brown, Matthew A., Croucher, P. I., Brown, S. D. M., Cox, R. D., Barber, A. H., Thakker, R. V., & Gupta, H. S. (2012) Significant deterioration in nanomechanical quality occurs through incomplete extrafibrillar mineralization in rachitic bone: Evidence from in-situ synchrotron X-ray scattering and backscattered electron imaging. Journal of Bone and Mineral Research, 27(4), pp. 876-890.

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Bone diseases such as rickets and osteoporosis cause significant reduction in bone quantity and quality, which leads to mechanical abnormalities. However, the precise ultrastructural mechanism by which altered bone quality affects mechanical properties is not clearly understood. Here we demonstrate the functional link between altered bone quality (reduced mineralization) and abnormal fibrillar-level mechanics using a novel, real-time synchrotron X-ray nanomechanical imaging method to study a mouse model with rickets due to reduced extrafibrillar mineralization. A previously unreported N-ethyl-N-nitrosourea (ENU) mouse model for hypophosphatemic rickets (Hpr), as a result of missense Trp314Arg mutation of the phosphate regulating gene with homologies to endopeptidase on the X chromosome (Phex) and with features consistent with X-linked hypophosphatemic rickets (XLHR) in man, was investigated using in situ synchrotron small angle X-ray scattering to measure real-time changes in axial periodicity of the nanoscale mineralized fibrils in bone during tensile loading. These determine nanomechanical parameters including fibril elastic modulus and maximum fibril strain. Mineral content was estimated using backscattered electron imaging. A significant reduction of effective fibril modulus and enhancement of maximum fibril strain was found in Hpr mice. Effective fibril modulus and maximum fibril strain in the elastic region increased consistently with age in Hpr and wild-type mice. However, the mean mineral content was ∼21% lower in Hpr mice and was more heterogeneous in its distribution. Our results are consistent with a nanostructural mechanism in which incompletely mineralized fibrils show greater extensibility and lower stiffness, leading to macroscopic outcomes such as greater bone flexibility. Our study demonstrates the value of in situ X-ray nanomechanical imaging in linking the alterations in bone nanostructure to nanoscale mechanical deterioration in a metabolic bone disease. Copyright

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ID Code: 89339
Item Type: Journal Article
Refereed: Yes
Keywords: bone matrix properties, in situ synchrotron small angle X-ray scattering, mineralization, N-ethyl-N-nitrosurea, nanomechanical imaging, X-linked hypophosphatemic rickets, collagen fibril, ethylnitrosourea, nanomaterial, proteinase, animal experiment, animal model, animal tissue, article, bone deformation, bone mineral, bone mineralization, bone stress, bone structure, deterioration, DNA sequence, elastic fiber, elasticity, female, femur, gene mapping, genotype, in vitro study, in vivo study, male, microradiography, missense mutation, molecular mechanics, mouse, muscle fibril, muscle strain, nonhuman, porosity, radiation scattering, radiography, rickets, rigidity, scanning electron microscopy, synchrotron, tensile strength, X chromosome, Amino Acid Sequence, Animals, Biomechanics, Bone and Bones, Calcification, Physiologic, Electrons, Hypophosphatemic Rickets, X-Linked Dominant, Mice, Mice, Inbred C57BL, Molecular Sequence Data, Mutation, Missense, Nanostructures, Phenotype, PHEX Phosphate Regulating Neutral Endopeptidase, Scattering, Small Angle, Stress, Mechanical, Synchrotrons, X-Rays
DOI: 10.1002/jbmr.1495
ISSN: 0884-0431
Divisions: Current > QUT Faculties and Divisions > Faculty of Health
Current > Institutes > Institute of Health and Biomedical Innovation
Copyright Owner: Copyright 2012 American Society for Bone and Mineral Research
Deposited On: 21 Oct 2015 02:21
Last Modified: 24 Feb 2016 02:32

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