Pre-existing osteoblasts are not required to trigger fracture healing

Fracture healing is a complex regenerative process. Although the histology and general mechanism of repair process are already clear and well established, much remains to be understood about the process of bone healing. The source of the cells that initiate fracture repair are unclear. It is thoght that fracture repair is initiated by mesenchymal progenitor cells (MPCs) which undergo differentiation into chondrocytes and osteoblasts, and produce cartilage and bone matrix respectively. At a later stage, the cartilage is completely replaced by bone, through endochondral ossification. Bone healing also occurs using intramembranous mechanism, that is, progenitors cells directly differentiate into osteoblasts and form new bone matrix [1]. Interestingly, even though it is well known that differentiated osteoblasts, whose major function is the production of bone matrix [2], are a crucial cell type during both intramembranous and endochondral bone formation in a healing process, it is not known yet whether preexisting osteoblasts at the time when fracture occurs can immediately participate to initiate this bone regeneration. To address this issue, we studied fracture repair in mice in which the Delta-Thymidine Kinase (DTK) gene is driven by an osteoblast specific type I collagen promoter. Treatment with ganacyclovir (GCV) results in ablation of osteoblast cells in these mice, and thus producses an osteoblast-deficient phenotype. .