Isefuku S, Joyner C J, Reed A A C, Simpson A H R W
Nuffield Department of Orthopaedic Surgery, University of Oxford, UK.
J Orthop Res. 2004 Nov;22(6):1276-82. doi: 10.1016/j.orthres.2004.04.009.
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.
牵张成骨术包括将一块骨头分开，并逐渐将骨端拉开。这会向牵张间隙中的间充质细胞传递机械刺激，在该间隙中，新骨主要通过膜内成骨再生。据报道，转录因子Cbfa1对于间充质细胞向成骨细胞的分化至关重要。在纯合Cbfa1基因敲除小鼠中，膜内和软骨内成骨机制均被阻断，且无骨形成。在杂合Cbfa1基因敲除小鼠中，只有通过膜内成骨形成的颅骨和锁骨，如同人类锁骨颅骨发育不全的情况一样，无法正常发育。因此，有人提出膜内成骨会受到一对Cbfa1基因中一个缺失的影响。我们评估了杂合Cbfa1基因敲除小鼠在牵张成骨术后膜内成骨的潜力。使用了14只骨骼成熟的雄性杂合小鼠以及10只野生型对照小鼠。用半环式固定器每天两次将胫骨牵张0.25毫米（每天0.5毫米），持续10天。9只小鼠再饲养28天以观察巩固期。在杂合组的5只小鼠中有4只以及所有3只野生型小鼠中，在X线片上观察到牵张间隙内有骨融合。在该过程的各个阶段，两组的组织学结果几乎相同，且两组均以膜内成骨为主。尽管在Cbfa1+/-小鼠的胎儿发育过程中膜内成骨受到抑制，但牵张成骨术与对照小鼠一样成功。
