Epigenetic Reprogramming to Enhance Bone Regeneration in Type 2 Diabetes

Type 2 diabetes is a highly prevalent chronic condition that affects Minnesotans' quality of life while also imparting a significant financial burden. A number of co-morbidities are associated with type 2 diabetes, including increased systemic inflammation, elevated bone fracture risk and diminished bone healing; thus, reducing the body's own ability to heal. Our work suggests that epigenetic reprogramming of innate immune cells enhances bone healing in pre-clinical, non-diabetic models. In this application, we propose to evaluate the effects of epigenetic reprogramming to bone healing in a high fat diet (HFD)-induced model of type 2 diabetes. We will also determine if epigenetic programming limits enhanced commitment to bone resorbing osteoclasts observed in type 2 diabetes and if a novel regulator of cellular metabolism, Lipocalin 2, controls innate immune cell responses and glucose utilization.