Notch Signaling in Bone Regeneration.

摘要

Over 26% of our military personnel injured in combat have severe fractures of their arms and legs. Civilians sustain similar injuries in motor vehicle collisions, falls, and after gun shot injuries. One of the goals of treatment is to have the body replace or restore lost bone. While bone usually heals without complication, about 10% of patients go on to have no healing or really slow healing. Over the past 20 years, knowledge of bone healing has increased with discovery and use of proteins and growth factors. However, there has been no description of the role of Notch signaling in fracture healing. Notch is involved in turning on cells that make bone and provide blood supply. We believe that by increasing the amount of Notch at a fracture site, injured bones in our military and civilian patients will heal better and faster. We will look at Notch in human and mouse fractures and enhance fracture healing by putting Notch on a special sponge to deliver it into an area of injury. We believe that developing tissue engineering applications to increase Notch signaling will promote healing, in combination with what surgeons are already doing. Once we show how Notch works in humans and enhance fracture healing in mice by increasing Notch delivery, a large animal model (e.g., sheep) could be developed and tested in another 2 years. Within five years, we will have a product to help soldiers on the battle field with fractures and bone defects. The risks of this therapy are low since Notch is normally produced in the body.