Assessment of the Genetic Variation in Bone Fracture Healing
Abstract:
The hypothesis of these studies is that genetic processes that lead to the variations in both structural and material properties of bone development will be recapitulated in the developmental mechanisms that controls the bone quality during fracture healing. Two goals were set out in this proposal to test this hypothesis. The first was to determine how variations in basic bone quality in the three in bred strains of mice were expressed during fracture healing. MicroCT and mechanical testing of day 21 and 35 fracture calluses demonstrated that each strain recapitulated their variations in geometric and material BMDBMC properties during fracture healing. Furthermore, variations in bone quality differentially effected the rates of healing i.e. there are genetic variations slow versus fast bone healing. The second goal was directed at identifying the underlying biological processes that lead to genetic variation, which effect both bone quality and rates of healing. Our data demonstrate that there is genetic variations in rates endochondral bone formation during fracture healing which recapitulate differences seen in original bone growthi.e. genetic strains that show slow or fast epiphyseal growth show slow or fast fracture healing. Large scale transcriptional profiling initiated during the tenure of this grant is ongoing to further define genetic variability in fracture healing.