The University of Alabama at Birmingham Birmingham United States
The proposal addresses a very important area of bone fracture healing that is a major health and financial burden in the United States. Towards developing an effective approach to cure segmental bone fractures, it is essential to understand additional mechanisms that play a crucial role in bone healing through participation of cells other than osteoblasts, osteoclasts and their respective progenitors. Bone fractures heal with overlapping phases of inflammation, cell proliferation, and bone remodeling. Osteogenesis and angiogenesis are known to work in concert to control many stages of this process, but when one is impaired, it leads to failure of fracture healing. During fracture repair, there is an abundant infiltration of immune cells at the fracture site that not only mediate the inflammatory responses, but also exert influence on neovasculature. The proposed studies will characterize the role of IMC in healing segmental bone fracture in tibia using an immunocompetent mouse model. Studies will encompass a detailed analysis of IMC function in bone healing through enhancement of cellular and molecular signals on endothelial cell invasion, migration and proliferation, aiding in proper ossification and healing. Overall, the studies will test the hypothesis that signals provided by IMC play a crucial role in interfacing sequential events of angiogenesis and osteogenesis that are vital for proper bone healing.