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Osteopontin deficiency increases bone fragility but preserves bone mass

Osteopontin deficiency increases bone fragility but preserves bone mass
Osteopontin deficiency increases bone fragility but preserves bone mass
The ability of bone to resist catastrophic failure is critically dependent upon the material properties of bone matrix, a composite of hydroxyapatite, collagen type I, and noncollagenous proteins. These properties include elastic modulus, hardness, and fracture toughness. Like other aspects of bone quality, matrix material properties are biologically-defined and can be disrupted in skeletal disease. While mineral and collagen have been investigated in greater detail, the contribution of noncollagenous proteins such as osteopontin to bone matrix material properties remains unclear. Several roles have been ascribed to osteopontin in the bone, many of which have the potential to impact material properties. To elucidate the role of osteopontin in bone quality, we evaluated the structure, composition, and material properties of bone from osteopontin-deficient mice and wild-type littermates at several length scales. Most importantly, the results show that osteopontin deficiency causes a 30% decrease in fracture toughness, suggesting an important role for OPN in preventing crack propagation. This significant decline in fracture toughness is independent of changes in whole bone mass, structure, or matrix porosity. Using nanoindentation and quantitative backscattered electron imaging to evaluate osteopontin-deficient bone matrix at the micrometer level, we observed a significant reduction in elastic modulus and increased variability in calcium concentration. Matrix heterogeneity was also apparent at the ultrastructural level. In conclusion, we find that osteopontin is essential for the fracture toughness of bone, and reduced toughness in osteopontin-deficient bone may be related to the increased matrix heterogeneity observed at the micro-scale. By exploring the effects of osteopontin deficiency on bone matrix material properties, composition and organization, this study suggests that reduced fracture toughness is one mechanism by which loss of noncollagenous proteins contribute to bone fragility
osteopontin, rodent, fracture toughness, bone matrix properties, mineralization
8756-3282
1564-1573
Thurner, Philipp J.
ab711ddd-784e-48de-aaad-f56aec40f84f
Chen, Carol
8f2bead7-a56d-4b78-94e3-a5ce39a04a1d
Ionova-Martin, Sophi
04580a17-f001-44fa-99bf-3259760c9407
Sun, Luling
dcc069cc-e52e-4f09-ab3c-c1fae8b84917
Harman, Adam
076eeee2-ba9f-4b49-85cf-da9aaec66ba4
Porter, Alexandra
79ecf94d-06a6-4dc5-ba95-8853e5d67b3e
Ager, Joel W.III
cc8a9c64-f37a-474a-a1f1-05f5f36ef5e0
Ritchie, Robert O.
aceaba6e-2424-4eee-ab05-bf81e85eb936
Alliston, Tamara
59ed06f9-d4e0-40ac-ac51-de474a743634
Thurner, Philipp J.
ab711ddd-784e-48de-aaad-f56aec40f84f
Chen, Carol
8f2bead7-a56d-4b78-94e3-a5ce39a04a1d
Ionova-Martin, Sophi
04580a17-f001-44fa-99bf-3259760c9407
Sun, Luling
dcc069cc-e52e-4f09-ab3c-c1fae8b84917
Harman, Adam
076eeee2-ba9f-4b49-85cf-da9aaec66ba4
Porter, Alexandra
79ecf94d-06a6-4dc5-ba95-8853e5d67b3e
Ager, Joel W.III
cc8a9c64-f37a-474a-a1f1-05f5f36ef5e0
Ritchie, Robert O.
aceaba6e-2424-4eee-ab05-bf81e85eb936
Alliston, Tamara
59ed06f9-d4e0-40ac-ac51-de474a743634

Thurner, Philipp J., Chen, Carol, Ionova-Martin, Sophi, Sun, Luling, Harman, Adam, Porter, Alexandra, Ager, Joel W.III, Ritchie, Robert O. and Alliston, Tamara (2010) Osteopontin deficiency increases bone fragility but preserves bone mass. Bone, 46 (6), 1564-1573. (doi:10.1016/j.bone.2010.02.014). (PMID:20171304)

Record type: Article

Abstract

The ability of bone to resist catastrophic failure is critically dependent upon the material properties of bone matrix, a composite of hydroxyapatite, collagen type I, and noncollagenous proteins. These properties include elastic modulus, hardness, and fracture toughness. Like other aspects of bone quality, matrix material properties are biologically-defined and can be disrupted in skeletal disease. While mineral and collagen have been investigated in greater detail, the contribution of noncollagenous proteins such as osteopontin to bone matrix material properties remains unclear. Several roles have been ascribed to osteopontin in the bone, many of which have the potential to impact material properties. To elucidate the role of osteopontin in bone quality, we evaluated the structure, composition, and material properties of bone from osteopontin-deficient mice and wild-type littermates at several length scales. Most importantly, the results show that osteopontin deficiency causes a 30% decrease in fracture toughness, suggesting an important role for OPN in preventing crack propagation. This significant decline in fracture toughness is independent of changes in whole bone mass, structure, or matrix porosity. Using nanoindentation and quantitative backscattered electron imaging to evaluate osteopontin-deficient bone matrix at the micrometer level, we observed a significant reduction in elastic modulus and increased variability in calcium concentration. Matrix heterogeneity was also apparent at the ultrastructural level. In conclusion, we find that osteopontin is essential for the fracture toughness of bone, and reduced toughness in osteopontin-deficient bone may be related to the increased matrix heterogeneity observed at the micro-scale. By exploring the effects of osteopontin deficiency on bone matrix material properties, composition and organization, this study suggests that reduced fracture toughness is one mechanism by which loss of noncollagenous proteins contribute to bone fragility

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More information

Published date: June 2010
Keywords: osteopontin, rodent, fracture toughness, bone matrix properties, mineralization
Organisations: Bioengineering Sciences

Identifiers

Local EPrints ID: 79719
URI: http://eprints.soton.ac.uk/id/eprint/79719
ISSN: 8756-3282
PURE UUID: fa178bc3-0f74-4d4d-a892-2c7ef57f9f41
ORCID for Philipp J. Thurner: ORCID iD orcid.org/0000-0001-7588-9041

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Date deposited: 19 Mar 2010
Last modified: 14 Mar 2024 00:32

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Contributors

Author: Carol Chen
Author: Sophi Ionova-Martin
Author: Luling Sun
Author: Adam Harman
Author: Alexandra Porter
Author: Joel W.III Ager
Author: Robert O. Ritchie
Author: Tamara Alliston

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