Effect of tension-stress on gene expression of one and cartilage cells. Molecular mechanism of distraction osteogenesis

我们最近建立了一个大鼠牵张成骨模型，并证明根据牵张的阶段，骨化模式从软骨内到膜内通过软骨状骨形成。本实验旨在探讨机械张力应力对牵张成骨相关细胞骨形态发生蛋白(BMP)-2、BMP-4和Runx2基因表达的影响。Runx2是一种存在于bmp下游的转录因子。它通过Runt结构域与DNA结合，在成骨细胞分化中起着重要作用。Northern blot分析和原位杂交结果显示，在机械拉力应力作用下软骨细胞高度表达Runx2基因和BMP-2、BMP-4基因。这些细胞似乎将其胶原表型从II型转换为I型，从而从软骨样细胞分化为成骨细胞。牵张完成后，延长节段未检测到BMP-2、BMP-4和Runx2。提示丰富的BMP-2、BMP-4基因产物可诱导丰富的Runx2，通过旁分泌和自分泌机制促进原位骨形成。

We have recently established a rat model of distraction osteogenesis, and demonstrated that the mode of ossification changed from endochondral to intramembranous via transchondroid bone formation depending on the stage of distraction. The present -study was designed to investigate the effect of mechanical tension-stress on gene expression of bone morphogenetic protein (BMP)-2 and BMP-4 and Runx2 by the cells involved in distraction osteogenesis. Runx2 is a transcription factor that exists in the downstream of BMPs. It bind to DNA through Runt- domain and plays an fundamental role in osteoblast differentiation. Northern blot analysis and in situ hybridization showed that Runx2 gene, as well as BMP-2 and BMP-4 genes, were highly expressed by the chondroid cells exposed to mechanical tension-stress. These cells seemed to switch their collagen phenotype from type II to type I to differentiate from chondroid cells into osteoblasts. After completion of distraction, none of BMP-2, BMP-4 and Runx2 were detected withm the lengthened segment. The present results suggest that abundant gene products of BMP-2, BMP-4 could induce abundant Runx2 and enhance the in situ bone formation by paracrine and autocrine mechanism.