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

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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.