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Age- and Diabetes-Related Changes in the Matrix and Fracture Resistance of Bone

dc.creatorCreecy, Amy
dc.description.abstractFracture resistance of bone depends on the hierarchical organization of its constituents, primarily the organic matrix, mineral, and water, and as such, requires characterization at multiple length-scales. The extracellular matrix of bone influences fracture resistance by promoting energy dissipation prior to breaking and inhibiting crack propagation. Aging and type 2 diabetes reduce bone quality independently of bone quantity, possibly through an accumulation of advanced glycation end-products (AGEs). However, it is not known how aging and type 2 diabetes affect bone matrix. Towards this goal, we have analyzed bone’s fracture resistance and matrix from preclinical models of type 2 diabetes and aging. Type 2 diabetes increased brittleness of cortical bone in a preclinical model. Higher tissue mineralization density and changes to the secondary structure of collagen could have resulted in the brittling of cortical bone. However, the brittleness phenotype did not progressively worsen with duration of diabetes. Aging lowered strength, toughness, and fracture toughness of cortical bone in a preclinical model. The bone matrix of older mice had higher mineralization density, altered collagen structure, higher enzymatic and non-enzymatic AGEs crosslinks, and lower bound water, all of which could have deleteriously affected fracture resistance. Furthermore, when analyzing proteins for post-translational modifications at specific sites, AGEs were found to be higher on specific residues of proteins from the matrix of older mice. Overall, matrix changes occur with aging and type 2 diabetes in preclinical models that have lower fracture resistance.
dc.subjectextracellular matrix
dc.subjecttype 2 diabetes
dc.titleAge- and Diabetes-Related Changes in the Matrix and Fracture Resistance of Bone
dc.contributor.committeeMemberDavid Merryman, Ph.D.
dc.contributor.committeeMemberMaureen Gannon, Ph.D.
dc.contributor.committeeMemberJeffery Davidson, Ph.D.
dc.contributor.committeeMemberJulie Sterling, Ph.D.
dc.contributor.committeeMemberMichael Miga, Ph.D.
dc.type.materialtext Engineering University
dc.contributor.committeeChairJeffry Nyman, Ph.D.

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