Periosteum plays a key role in bone repair through activation of residing
stem and/or progenitor cells. The molecular signals regulating differentiation
and expansion of periosteal stem cells during early repair are poorly
understood. Understanding the molecular basis for initiation and completion of
bone healing is vital for the success of bone-tissue engineering and
regeneration therapy for impaired bone healing. We established a
live-bone-graft transplantation model that allows us to quantitatively
evaluate the fate of the periosteal cells and cell-initiated endochondral bone
healing with use of a transgenic and knockout mouse model. By combining this
live-bone-graft transplantation method with a tamoxifen-inducible
CreER-mediated gene recombination model (R26CreER), we developed a novel
approach to efficiently delete genes in periosteal cells during the initiation
of skeletal repair. This approach allows us to use floxed mice to examine the
function of genes whose germline deletion results in lethality during
development. Successful bone repair and regeneration therapies require a
deeper understanding of the signals and signaling pathways that are critical
for the morphogenesis of the repair tissues. Early lethality in genetically
manipulated mice prohibits an understanding of the function of genes in the
adult repair process. Our current approach overcomes this encumbrance and
enables examination of gene function in a time-dependent and
repair-tissue-specific manner.