Cell Differentiation in Periodontal Regeneration

描述（由申请人提供）：创伤以及先天性疾病导致口腔颌面部骨和软组织缺损。 牙周病导致牙槽骨破坏和牙齿脱落。这些疾病的最终治疗目标是组织再生，这需要（1）修复细胞的分化和（2）细胞外基质组分的产生。我们的长期目标是扩大目前对牙周组织形成和再生所涉及的细胞和分子机制的理解，并为骨骼再生和组织工程产品的开发提供进一步的见解。本申请的目的是确定参与组织修复和再生过程的细胞的分化潜能。待检验的中心假设是，在牙周再生中，转录因子Cbfa1选择性诱导成骨和牙骨质分化以及随后的BSP表达，其增强组织形成和矿化。其基本原理是基于以下证据：未分化的间充质细胞和前成骨细胞转化为成熟和功能性成骨细胞是骨形成以及骨再生的关键步骤。 目标1.确定在体内的调节和促进作用，Cbfa 1在牙周再生过程中发生的细胞分化。使用基因治疗的方法，第一次，“主基因”Cbfa 1，将被引入到一个人工创建的牙周缺损和其诱导和调节作用的记录。 目标二。目的：探讨骨基质蛋白（BSP）在骨组织形成和再生过程中的作用。使用基于细胞的方法，将BSP过表达细胞移植到牙周缺损中，并首次确定BSP在体内增强生物矿化和骨成熟的效果。 这些深入研究的结果应该为成骨基因治疗和细胞分化的分子控制提供新的重要见解，细胞分化是组织形成和牙周再生中最重要的组成部分和最强大的引擎。

DESCRIPTION (provided by applicant): Traumas as well as congenital disorders cause bone and soft tissue defects in oral and maxillofacial region. Periodontal disease results in destruction of alveolar bone and tooth loss. The ultimate therapeutic goal for these diseases is tissue regeneration, which requires (1) differentiation of reparative cells and (2) production of extracellular matrix components. Our long-range goal is to expand current understanding of the cellular and molecular mechanisms involved in formation and regeneration of periodontal tissues and to provide further insight into the development of products for skeletal regeneration and tissue engineering. The objective of this application is to determine differentiation potential of cells involved in the processes of tissue repair and regeneration. The central hypothesis to be tested is that, in periodontal regeneration, the transcription factor Cbfa1 selectively induces osteogenic and cementogenic differentiation and the subsequent expression of BSP which enhances tissue formation and mineralization. The rationale is based on evidence that the conversion of non-differentiated mesenchymal cells and pre-osteoblastic cells into mature and functional osteoblasts is a crucial step in bone formation, as well as in bone regeneration. Aim 1. To determine in vivo the regulating and promoting effects of Cbfa1 in cell differentiation occurring during periodontal regeneration. Using a gene-therapy approach, for the first time, the "master gene" Cbfa1, will be introduced into an artificially created periodontal defect and its inductive and modulating effects documented. Aim 2. To determine the role of BSP expressed by differentiated cells in enhancing mineralization in the process of bone tissue formation and regeneration in rive. Using a cell-based method, BSP overexpressing cells will be transplanted into periodontal defects and for the first time the effect of BSP in enhancing biomineralization and bone maturation in vivo determined. Results derived from these in rive studies should provide novel and important insights into osteogenic gene therapy and molecular control of differentiation of cells, the most important component and the most powerful engine in tissue formation and periodontal regeneration.