Fate, origin and roles of cells within free bone grafts

The efficacy of autologous bone grafting in repairing nonunion fractures, large bone defects and spinal instability is widely accepted. However, the cellular and molecular mechanisms underlying new bone formation in bone grafting have yet to be fully elucidated. The purpose of this study was to clarify the fate, origin and the contribution of the cells within the grafted bone. This study was designed to investigate the role and fate of cells contained in the grafted bone and their contribution to new bone formation in the graft in an animal model. Middiaphyseal cylindrical bone samples obtained from green fluorescent protein (GFP) transgenic and wild-type rats were transplanted into the back muscle of wild-type and GFP rats, respectively. The transplanted bones were evaluated by immunohistochemistry, in situ hybridization and quantitative reverse transcription polymerase chain reaction. Immunohistochemical analyses showed that all the cells in the newly formed bone originated from the grafted bone, and osteoblasts were gradually replaced by host cells. Conversely, osteoclasts were immediately replaced by host cells 2 weeks after the bone graft. In addition, expression of bone morphogenetic protein (Bmp)-4, Bmp receptors and Noggin in the grafted bone was significantly upregulated before new bone formation occurred, indicating that the grafted cells might contribute to the recruitment of mesenchymal cells into the graft bed. This study revealed the possible molecular mechanisms of the contribution of cells contained in grafted bone to facilitate new bone formation.