Transcription factor osterix modified bone marrow mesenchymal stem cells enhance callus formation during distraction osteogenesis

This study was designed to investigate the effects of local delivery of bone marrow mesenchymal stem cells (BMMSCs) with or without osterix (OSX) gene transfected on bone regeneration in the distracted zone using a rabbit model of mandibular lengthening. Fifty-four New Zealand white rabbits underwent osteodistraction of the left mandible and were then randomly divided into group A, group B, and group C (n = 18 for each group). At the end of distraction BMMSCs transfected with OSX, autologous BMMSCs and physiological saline were injected into the distraction gaps in groups A, B, and C, respectively. Nine animals from each group were humanely killed at 2 and 6 weeks after completion of distraction. The distracted mandibles were harvested and processed for radiographic, histological, and immunohistochemical examination. Excellent bone formation in the distracted callus was observed in group A and group B; the former showed better bone formation and highest bone mineral density (BMD), thickness of new trabeculae (TNT, mm) and volumes of the newly formed bone area (NBV) in the distraction zones. Group C animals showed poor bone formation in the distracted callus when compared with groups A and B. Positive immunostaining of bone sialoprotein (BSP) was observed in the distracted callus in all groups; however, BSP expression was much stronger in group A than in groups B and C. The results of this study suggest transplantation of BMMSCs can promote bone formation in DO; OSX-mediated ex vivo gene therapy was more effective during bone deposition and callus formation in distraction osteogenesis.