正畸牙移动牵张侧出现新骨形成的机制尚未明确。CREB是一种磷酸化依赖性的转录因子，调控多种细胞生长因子及趋化因子的表达。项目组前期研究发现，CREB磷酸化特异性发生在小鼠正畸牙移动模型牵张侧的牙周膜细胞中，同时体外模型中周期性张应力的牙周膜细胞CREB表达及磷酸化水平上调。项目组提出假设：牙周膜细胞CREB磷酸化在正畸牙移动牵张侧的成骨过程中发挥重要作用。通过生物信息学预测结合表达谱芯片结果sdf1、fgf2为CREB潜在靶基因。首先检测体内外牙周膜牵张应力条件下CREB的表达及磷酸化，检测sdf1、fgf2表达，分析CREB磷酸化与sdf1、fgf2的相关性；分别在牙周膜细胞中过表达CREB和抑制CREB后检测牙周膜细胞条件培养基对骨髓基质细胞迁移、成骨向分化的作用，检测下游潜在靶基因sdf1、fgf2表达。进一步用双荧光素酶实验、染色体免疫共沉淀实验检测CREB对靶基因结合与调控作用。

Teeth are moved through alveolar bone by the application of adequate orthodontic forces，but the exact mechanism of the bone formation in the tensile side is still unclear. CREB is a kind of phosphorylation-dependent transcription factors, which was proved to regulate the expression of vast number of growth factors and cytokines. Our preliminary study found that the expression and phosphorylation of CREB is specifically upregulated in the periodontal ligament cells (PDLs) of the tensile side during tooth movement. We raise a hypothesis that phosphorylation of CREB in the tensile side may regulate bone formation during orthodontic tooth movement. Based on bioinformatics methods and micro-array results, potential CREB target genes were chosen. Firstly, the expression patterns of CREB, P-CREB and potential CREB target gene in the PDLs under tensile force were detected in vivo and in vitro. Secondly, CREB was activated or inhibited by overexpression of constitutive CREB or dominant negative CREB in the PDLs. And the expression of the potential CREB target genes is detected by RT-PCR and western blot. Induction of BMSC migration and osteogenic differentiation are detected by transwell and induction medium. Furthermore, are used to predict its downstream target gene. The binding interaction between p-CREB and its target genes will be further confirmed by dual luciferase assay, EMSA and ChIP assay. This study will help to understand function of PDLs expressed CREB in bone formation during orthodontic tooth movement.