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    [[The]] role of extra-cellular matrix proteins and post-translational modifications on bone fracture

    Author
    Bailey, Stacyann Morgan
    View/Open
    177861_Bailey_rpi_0185E_10975.pdf (2.399Mb)
    Other Contributors
    Vashishth, Deepak; Corr, David T.; Carpenter, Caren G; Ledet, Eric H.;
    Date Issued
    2016-12
    Subject
    Biomedical engineering
    Degree
    PhD;
    Terms of Use
    This electronic version is a licensed copy owned by Rensselaer Polytechnic Institute, Troy, NY. Copyright of original work retained by author.;
    Metadata
    Show full item record
    URI
    https://hdl.handle.net/20.500.13015/1843
    Abstract
    Finally, the contribution of PTMs to bone fracture in a type-II diabetic model was evaluated. Obesity-induced diabetes resulted in an increase in the amount of non-enzymatic cross-links and an associated reduction in bone propagation toughness. This project provides an understanding of the role of bone matrix proteins and their modifications on bone size, shape, strength, and fracture.; Osteocalcin (OC) and osteopontin (OPN) are major NCPs in bone matrix. They exhibit multifunctional roles that are critical in the determination of bone quality and bone’s structural integrity against fracture. In this study, using genetically modified mice, we show that OC and OPN synergistically influence bone size, shape and strength. Post-translational modifications (PTMs) of these bone matrix proteins can be detrimental to bone quality. Protocols developed for in-vitro PTMs of whole bone were applied to OC and OPN knockout mice and bone material properties assessed using fracture mechanics. The results show that glycated OC contributes to loss of bone toughness and phosphorylation of OPN increases bone fracture resistance.; Bone is a complex structural material that deteriorates in quality with age and disease. As a result, bone is unable to perform its critical mechanical function leading to fracture. Clinically, diagnosis of osteoporosis and the susceptibility to fracture are determined by Bone Mineral Density (BMD). However, multiple factors in addition to BMD contribute to the fracture resistance of bone such as the quality and composition of bone’s primary constituents. These constituents are hydroxyapatite mineral, type I collagen and non-collagenous proteins (NCPs). Consequently, the spatial arrangement of these nanoscale elements determines the mechanical properties of bone. Nevertheless, the contribution of NCPs in the determination of bone quality and fracture remains largely undefined.;
    Description
    December 2016; School of Engineering
    Department
    Dept. of Biomedical Engineering;
    Publisher
    Rensselaer Polytechnic Institute, Troy, NY
    Relationships
    Rensselaer Theses and Dissertations Online Collection;
    Access
    Restricted to current Rensselaer faculty, staff and students. Access inquiries may be directed to the Rensselaer Libraries.;
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    • RPI Theses Online (Complete)

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