Abnormal Mineral-Matrix Interactions Are a Significant Contributor to Fragility in oim/oim Bone

Miller, Elizabeth A.; Delos, Demetris; Baldini, Todd; Wright, Timothy M.; Camacho, Nancy P.

doi:10.1007/s00223-007-9045-x

Cited by 42 publications

(36 citation statements)

References 52 publications

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“…The association of dilatational bands with damage at higher scales, including diffuse damage, explains their contribution to bone toughness. Thus, any changes in bone's nanostructure (i.e., mineral, collagen, and noncollagen proteins), reported in osteoporosis and metabolic bone diseases (45)(46)(47)(48)(49), will dramatically reduce bone toughness by altering toughening at from nano-to macro scales.…”

Section: Discussionmentioning

confidence: 99%

Dilatational band formation in bone

Poundarik

Diab

Sroga

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

238

274

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Toughening in hierarchically structured materials like bone arises from the arrangement of constituent material elements and their interactions. Unlike microcracking, which entails micrometer-level separation, there is no known evidence of fracture at the level of bone's nanostructure. Here, we show that the initiation of fracture occurs in bone at the nanometer scale by dilatational bands. Through fatigue and indentation tests and laser confocal, scanning electron, and atomic force microscopies on human and bovine bone specimens, we established that dilatational bands of the order of 100 nm form as ellipsoidal voids in between fused mineral aggregates and two adjacent proteins, osteocalcin (OC) and osteopontin (OPN). Laser microdissection and ELISA of bone microdamage support our claim that OC and OPN colocalize with dilatational bands. Fracture tests on bones from OC and/or OPN knockout mice (OC −/− , OPN −/− , OC-OPN −/−;−/− ) confirm that these two proteins regulate dilatational band formation and bone matrix toughness. On the basis of these observations, we propose molecular deformation and fracture mechanics models, illustrating the role of OC and OPN in dilatational band formation, and predict that the nanometer scale of tissue organization, associated with dilatational bands, affects fracture at higher scales and determines fracture toughness of bone.noncollagenous proteins | diffuse damage | energy dissipation I n hierarchically structured materials, the composition and spatial arrangement of nanoscale elements are the key determinants of toughness (1, 2). In comparison with many man-made materials, cortical bone is well known for its superior toughness (3, 4). Bone's ability to resist crack propagation originates from its highly complex hierarchical material structure ( Fig. 1). At the highest level of material structure in adult human bone lie the osteons (0.1-0.2 mm in diameter) that contribute to toughness by trapping microcracks (5, 6) and participate in the formation of "uncracked ligaments" (7). Osteons are made of multiple 3-to 7-μm-thick sheets (lamellae) of mineralized matrix. Individual lamellae have the ability to slide past each other (8, 9), forming 60-to 130-μm-long linear microcracks (9) that provide resistance to fracture through microcrack toughening (10). Individual mineralized collagen fibrils <1μm thick, which make up the lamellae, bridge the crack surfaces and toughen the bone (7). Bone's ability to crack, and not fracture by propagating that crack, is therefore a key fundamental aspect of the toughening mechanisms at the microstructural level (10).Recent evidence suggests that bone's nanostructure contributes to bone toughness (11). The nonfibrillar and ductile extrafibrillar matrix components in bone can serve as a "glue" between stiffened mineralized collagen fibrils (11) and between fibrils and mineral platelets (12). Fibril matrix shearing (13) has been proposed to enhance bone toughness through mineral interparticle friction (14) and "sacrificial bonds," a nanoscale mechanism...

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Section: Discussionmentioning

confidence: 99%

Dilatational band formation in bone

Poundarik

Diab

Sroga

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

238

274

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“…Reduced bone size [7,8,13,17,18] and generally brittle mechanical behavior at both the tissue and structural levels has also been observed [7,10,13,14,17,19].…”

Section: Introductionmentioning

confidence: 94%

Multi-scale analysis of bone chemistry, morphology and mechanics in the oim model of osteogenesis imperfecta

Bart

Hammond

Wallace

2014

Connective Tissue Research

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Osteogenesis imperfecta is a congenital disease commonly characterized by brittle bones and caused by mutations in the genes encoding Type I collagen, the single most abundant protein produced by the body. The oim model has a natural collagen mutation, converting its heterotrimeric structure (two α1 and one α2 chains) into α1 homotrimers. This mutation in collagen may impact formation of the mineral phase, creating a brittle bone phenotype in this animal. Femurs from male wild type (WT) and homozygous (oim/oim) mice, all at 12 weeks of age, were assessed using assays at multiple length scales with minimal sample processing to ensure a near-physiological state. Atomic force microscopy (AFM) demonstrated detectable differences in the organization of collagen at the nanoscale that may partially contribute to alterations in material and structural behavior obtained through mechanical testing and reference point indentation (RPI). Changes in geometric and chemical structure obtained Multi-scale analyses of this nature offer much in assessing how molecular changes compound to create a degraded, brittle bone phenotype.

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“…Changes in the size and shape of mineral crystals in bone (e.g. less organized, more round-shaped crystals) have also been reported [18][19][20], which might be related to a change in the ability of tropocollagen to bind to the mineral phase of bone [21,22]. At larger length-scales, the effects of osteogenesis imperfecta mutations lead to inferior mechanical properties of tendon and bone [23].…”

Section: Mechanics Of Structural Materials In Disease Statesmentioning

confidence: 99%

Multiscale mechanics of biological and biologically inspired materials and structures

Buehler

2010

Acta Mechanica Solida Sinica

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Abstract:The world of natural materials and structures provides an abundance of applications in which mechanics is a critical issue for our understanding of functional material properties. In particular, the mechanical properties of biological materials and structures play an important role in virtually all physiological processes and at all scales, from the molecular and nanoscale to the macroscale, linking research fields as diverse as genetics to structural mechanics in an approach referred to as materiomics. Example cases that illustrate the importance of mechanics in biology include mechanical support provided by materials like bone, the facilitation of locomotion capabilities by muscle and tendon, or the protection against environmental impact by materials as the skin or armors. In this article we review recent progress and case studies, relevant for a variety of applications that range from medicine to civil engineering. We demonstrate the importance of fundamental mechanistic insight at multiple time-and lengthscales to arrive at a systematic understanding of materials and structures in biology, in the context of both physiological and disease states and for the development of de novo biomaterials. Three particularly intriguing issues that will be discussed here include: First, the capacity of biological systems to turn weakness to strength through the utilization of multiple structural levels within the universality-diversity paradigm. Second, material breakdown in extreme and disease conditions. And third, we review an example where the hierarchical design paradigm found in natural protein materials has been applied in the development of a novel biomaterial based on amyloid protein.

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Abnormal Mineral-Matrix Interactions Are a Significant Contributor to Fragility in oim/oim Bone

Cited by 42 publications

References 52 publications

Dilatational band formation in bone

Dilatational band formation in bone

Multi-scale analysis of bone chemistry, morphology and mechanics in the oim model of osteogenesis imperfecta

Multiscale mechanics of biological and biologically inspired materials and structures

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