Abstract
Diabetes, either Type 1 or Type 2, is linked with higher risk of bone fractures. The degradation of bone tissue quality, independent of changes in bone mineral density, is a key factor contributing to this vulnerability. A primary indicator of poor bone quality is the accumulation of irreversible crosslinks known as advanced glycation end-products (AGEs), resulting from non-enzymatic glycation of proteins. These AGEs have been shown to induce dysfunction in bone cells, particularly osteocytes. The abnormalities at the cellular level are likely to translate to poor bone tissue quality and ultimately degrade the mechanical properties of the skeletal system at higher levels. At the tissue level, the accumulation of these harmful compounds differs among distinct bone tissue types (cortical and trabecular), but there are contradictory reports in the literature on how they differ. However, bone tissue defects due to AGEs accumulation are evident and may be mitigated by anti-glycation inhibitors such as dietary supplements (vitamins). Therefore, the overall goal of this project is to evaluate the rate of AGEs accumulations in different types of diabetes and different bone tissue types, along with evaluating the inhibition of glycation on both tissue and cellular level. Our research aims to address three pivotal objectives: 1) to compare AGEs accumulation in cortical versus trabecular bone and in Type 1 versus Type 2 diabetic bone, 2) to investigate the impact of glycation inhibitors, Vitamin B and Vitamin C, on cortical bone tissue, and 3) to investigate the impact of glycation inhibitors, Vitamin B and Vitamin C, on osteocytes grown in high glucose. Our results highlight the accumulation of AGEs in bone with negative impacts of hyperglycemia on both tissue and osteocyte bone cells, with possible anti-glycation effects due to Vitamin B and C.