Distraction osteogenesis in the Cbfa-1 +/− mouse

Abstract

Distraction osteogenesis involves division of a bone and gradually pulling the bone ends apart. This delivers mechanical stimulation to mesenchymal cells in the distraction gap, where new bone is regenerated predominantly by intramembranous ossification. The transcription factor Cbfa1 has been reported to be essential for the differentiation of mesenchymal cells to osteoblasts. In homozygous Cbfa1 knockout mice, both intramembranous and endochondral ossification mechanisms are blocked and no bone formation occurs. In heterozygous Cbfa1 knockout mice, only the cranial bones and the clavicles, which form through intramembranous ossification, fail to develop properly as in the human condition of cleidocranialdysostosis. It has been suggested, therefore, that intramembranous ossification is affected by the absence of one of the paired Cbfa1 genes. We have assessed the potential for intramembranous ossification following distraction osteogenesis in heterozygous Cbfa1 knockout mice. Fourteen skeletally mature male heterozygous mice were used, together with 10 wild-type controls. The tibia was distracted by 0.25 mm twice a day (0.5 mm/day) for 10 days using the half-ring type fixator. Nine mice were kept for a further 28 days to observe the consolidation phase. In four out of five mice of the heterozygous group and in all three wild-type mice, bony fusion within the distraction gap was observed on radiographs. Histological findings were almost the same in the two groups at various stages of the procedure and intramembranous ossification was predominant in both the groups. Despite the inhibition of intramembranous ossification during the foetal development of Cbfa1 +/− mice, distraction osteogenesis was as successful as in control mice.