Regulatory mechanism of MMPs expression in periodontal ligament cells induced by mechanical stress

本研究的目的是阐明哪些MMPs参与了牙齿移动过程中牙周组织的改建，以及MMPs的表达和激活是如何受到调控的。特别是直接诱导任何MMPs的基因表达将是重点，而不仅仅是验证通过细胞因子信号传导的间接途径.我们采用动物模型系统，阐明在牙齿移动过程中的组织学变化和MMPs的基因表达模式的变化，通过原位杂交方法。结果：1.发现MMP-2、MMP-8和MMP-13在PDL细胞中的表达瞬时增强，而MMP-9仅在破骨细胞中表达.人牙周膜细胞受到两种不同类型的机械应力;张力和压缩力，并表现出相似的模式的mRNA表达。MMP-1和MMP-2表达上调。膜型MMP、MT 1-MMP的表达水平在机械应力作用下无明显变化。本实验中未检测到MMP-9。只有TIMP-1 mRNA水平在机械应力后保持稳定。TIMP-1、TIMP-2 mRNA表达水平上调。mRNA表达水平的变化与前列腺素E2处理后mRNA水平的变化规律相似。诱导型前列腺素合酶（考克斯-2）mRNA的表达也被机械应力上调。

The purpose of this investigation is to clarify which MMPs are involved in the periodontal tissue remodeling during tooth movement and how the expression and activation of MMPs are regulated. Especially, direct induction of gene expression of any MMPs will be focused on, not only verify the indirect pathway through cytokine signaling.1. We employed an animal model system to elucidate the histological changes during the tooth movement and changes in the gene expression patterns of MMPs by using in situ hybridization method. We found that the expression of MMPs-2, -8 and -13 were transiently promoted in the PDL cells, while the MMP-9 is only expressed in the osteoclasts.2. Human PDL cells were subjected to two different type of mechanical stress ; tension-force and compressive-force, and showed similar pattern of mRNA expression. MMP-1 and -2 were up-regulated. Membrane type MMP, MT1-MMP was also detectable, and its expression level was not changed by mechanical stress. MMP-9 was not detected in this experiment. Only TIMP-1 mRNA Level was stable after mechanical stress. On the other hand, mRNA expression levels of TIMP-1, -2 were up-regulated. The changes of mRNA expression level showed similar pattern with the changes of mRNA level by the treatment of prostaglandin E2. Inducible prostaglandin synthase, COX-2 mRNA expression was also up-regulated by mechanical stress.