Biomolecular and Cellular Mechanisms of Diabetic Skeletal Fragility

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Project Summary/Abstract This proposal includes a supplementary research plan that allows for successful completion of the PI’s original 5-year K01 project. The PI is currently an Assistant Professor in the Department of Bioengineering at the University of Massachusetts Dartmouth and a formal Research Collaborator at the Center for Advanced Orthopaedic Studies (CAOS) at Beth Israel Deaconess Medical Center (BIDMC). She is well supported by her institution and devotes 75% effort to this project. The PI has mentors and collaborators with a wide array of expertise to help her conduct her work and offer career guidance during this project. Her mentors and collaborators have expertise in biomechanics, clinical issues in diabetes, cell and tissue culture methods, high- resolution imaging, and molecular biology techniques. This project focuses on the causes of skeletal fragility in type 2 diabetes, which are largely unknown. Deficits in bone matrix via the accumulation of advanced glycation end-products and/or microarchitecture have been suggested to be potential mechanisms. The overall goal of this project is to determine the underlying biomolecular and cellular mechanisms of diabetic skeletal fragility with a specific focus during this supplemental 6-month period to successfully complete two of her original aims. These two aims are: A) to determine the contribution of advanced glycation end-products, microdamage, and cortical porosity to diabetic skeletal fragility, and B) to determine the effect of hyperglycemia and non-enzymatic glycation on osteocyte activity. The candidate has already trained in several brand-new skills including measurement of gene expression, cell and tissue culture methods, and other molecular biology related technologies as part of her originally awarded K01 project. This K01 supplemental proposal will provide her with additional time and resources (needed due to COVID-19 pandemic-related research hindrances) to successfully achieve these goals.