Abstract
The prevalence of type 2 diabetes (T2D) is rapidly growing due to increased obesity resulting from changing lifestyles. Thus, T2D has become a major health concern with more than 400 million people affected worldwide. Furthermore, the risk of osteoporotic bone fractures is increased in diabetic patients, and bone fragility has been recently recognized as a major diabetic complication. Because the fracture risk is independent of any change in bone mineral density, it is likely that the deterioration of bone tissue quality is one key cause of bone fragility. Among the components of poor bone quality are the accumulation of collagen cross-links known as advanced glycation end-products (AGEs). AGEs are a kind of irreversible chemical product that result from non-enzymatic glycation of proteins. AGEs are known to affect bone mechanical properties by changing the properties of collagen and cause dysfunction of bone cells such as osteocytes, although the mechanisms remain poorly understood. Our goal is to investigate how diabetes-related factors such as chronic hyperglycemia and glycation affect the function of osteocytes, and if metformin, a commonly prescribed diabetic drug is beneficial to these cells, using the novel OCY454 cell line. We hypothesize that hyperglycemia and AGEs negatively impact bone quality, and that this occurs by increasing bone resorption markers and inflammatory markers in osteocytes. We also hypothesize that metformin via its anti-glycemic and antiglycation properties, inhibits the induced inflammatory response and helps in maintaining the bone remodelling process in osteocytes. This work will allow us to differentiate between hyperglycemia induced and AGEs induced response in osteocytes, and to check the effectiveness of metformin in inhibiting these responses to improve the cellular function of osteocytes. Overall, this work will help to understand how osteocytes play a role in increased fracture risk in diabetic patients to develop treatment therapies that prevent the formation of AGEs for clinical management of diabetic patients.