Clarification of the mechanisms of regeneration of periodontal ligament using human clonal periodontal ligament progenitor cell line

在本项目中，我们建立了两个克隆的人牙周膜(PDL)干/祖细胞系，并将其鉴定为负责牙周膜再生的细胞元件。虽然这两个细胞系表达与骨髓间充质干细胞相同的表面标志，但这些细胞系特异性地包括PDL组织特有的Periostin和Skeraxis。含钙成分的材料作为支架元素，能有效地诱导这两种未分化细胞向成牙骨质/成骨细胞分化。此外，我们还阐明了碱性成纤维细胞生长因子和转化生长因子-β-1作为信号元件在牙周膜再生中的作用。血管紧张素II在心血管系统调节中起重要作用，对组织再生有重要影响。我们还揭示了PDL干/祖细胞的功能，表明我们开发的细胞系分泌神经生长因子来诱导神经分化、神经迁移和抑制神经细胞的凋亡。这些结果表明，PDL的组织再生是通过这三个要素的功能结合来实现的。

In this project, we have developed two clonal human periodontal ligament (PDL) stem/progenitor cell lines, and characterized them as cell elements responsible for PDL regeneration. Although both of cell lines expressed the same surface markers as bone marrow-derived mesenchymal stem cells, these cell lines specifically included Periostin and Scleraxis specific for PDL tissues. As scaffold elements, the materials containing calcium components effectively induced the differentiation of these two undifferentiated cell lines into cementoblastic/osteoblastic cells. Furthermore, as signaling elements, we clarified the efficacies of Basic Fibroblast Growth Factor and Transforming Growth Factor-β1 in PDL regeneration. And Angiotensin II that played important roles in regulating cardiovascular systems was suggested to affect tissue regeneration valuably. We also disclosed the functions of PDL stem/progenitor cells, indicating that our developed cell lines secreted Nerve Growth Factor to induce the neural differentiation, and neural migration, and inhibit apoptosis of neural cells. These results suggested that PDL tissue regeneration was accomplished by combining these three elements functionally.