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

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Abstract

The presence of abnormal type I collagen underlies the tissue fragility in the heritable disease osteogenesis imperfecta (OI), though the specific mechanism remains ill-defined. The current study addressed the question of how an abnormal collagen-based matrix contributes to reduced bone strength in OI by comparing the material properties of mineralized and demineralized bone from the oim/oim mouse, a model of OI that contains homotrimeric (α13(I)) type I collagen, with the properties of bone from wildtype (+/+) mice. Femoral three-point bend tests combined with geometric analyses were conducted on intact (mineralized) 14-week-old oim/oim and +/+ mice. To investigate the bone matrix properties, tensile tests combined with geometric analyses were conducted on demineralized femora. The majority of the properties of the mineralized oim/oim bone were inferior to those of the +/+ bone, including greater brittleness (+78.6%) and lower toughness (–69.2%). In contrast, tensile measurements on the demineralized bone revealed no significant differences between the oim/oim and +/+ bone, indicating that the matrix itself was not brittle. These results support the concept that deficient material properties of the demineralized bone matrix itself are not the principal cause of the severe fragility in this model of OI. It is likely the abnormal collagen scaffold serves as a template for abnormal mineral deposition, resulting in an incompetent mineral-matrix interaction that contributes significantly to the inferior material properties of bone in oim/oim mice.

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Acknowledgments

This study was supported by NIH DE11803 and AR48337 (NPC), and utilized the facilities of the Core Center for Skeletal Integrity NIH AR46121.

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Author notes

  1. Elizabeth Miller

    Present address: New York University School of Medicine, 530 First Avenue, New York, NY, 10016, USA

  2. Todd Baldini

    Present address: UCHSC @ Fitzsimons, 13001 E. 17th Place, Bldg. 500, Rm. NG005, Aurora, CO, 80010, USA

Authors and Affiliations

  1. Musculoskeletal Integrity Program, Research Division, Hospital for Special Surgery, 535 E. 70th Street, New York, NY, 10021, USA

    Elizabeth Miller, Demetris Delos, Timothy M. Wright & Nancy Pleshko Camacho

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  1. Elizabeth Miller
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Correspondence to Nancy Pleshko Camacho.

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Miller, E., Delos, D., Baldini, T. et al. Abnormal Mineral-Matrix Interactions Are a Significant Contributor to Fragility in oim/oim Bone. Calcif Tissue Int 81, 206–214 (2007). https://doi.org/10.1007/s00223-007-9045-x

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  • DOI: https://doi.org/10.1007/s00223-007-9045-x

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