Development of a multipotent clonal human periodontal ligament cell line
Development of a multipotent clonal human periodontal ligament cell line
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DOI：
10.1111/j.1432-0436.2007.00233.x
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发表时间：
2008-04-01
期刊：
影响因子：
2.9
通讯作者：
Akamine, Akifumi
中科院分区：
文献类型：
--
作者：
Tomokiyo, Atsushi;Maeda, Hidefumi;Akamine, Akifumi
牙周膜（PDL）将牙根固定到牙槽骨上，影响牙齿的寿命，而牙周炎导致的PDL损失很难再生。新的PDL再生疗法的开发需要PDL干细胞的分离。然而，由于体细胞PDL干细胞系的缺乏和PDL由异质细胞群组成，它们的特征尚不清楚。最近，我们成功地永生化人PDL成纤维细胞，保留了原代细胞的特性。因此，我们的目的是建立一个人牙周膜定向干细胞系，并探讨碱性成纤维细胞生长因子（bFGF）对细胞的成骨分化的影响。在这里，我们报告的发展细胞系1-17，多能克隆人PDL细胞系，表达胚胎干细胞相关的多能性基因Oct 3/4和Nanog，以及PDL相关分子periostin和scleraxis。在成骨细胞诱导培养基中用bFGF连续处理细胞系1-17抑制其钙化，下调FGF-受体1（FGF-R1）的表达，而随后加入bFGF增强其钙化。此外，bFGF诱导钙化的细胞系1-17时，它与成骨细胞共培养。这些结果表明，细胞系1-17是PDL定向干细胞系，并且bFGF发挥二元（即，促进和抑制）对基于其分化阶段的细胞系1-17的成骨分化的作用。
The periodontal ligament (PDL) that anchors the tooth root to the alveolar bone influences the lifespan of the tooth, and PDL lost through periodontitis is difficult to regenerate. The development of new PDL-regenerative therapies requires the isolation of PDL stem cells. However, their characteristics are unclear due to the absence of somatic PDL stem cell lines and because PDL is composed of heterogeneous cell populations. Recently, we succeeded in immortalizing human PDL fibroblasts that retained the properties of the primary cells. Therefore, we aimed to establish a human PDL-committed stem cell line and investigate the effects of basic fibroblast growth factor (bFGF) on the osteoblastic differentiation of the cells. Here, we report the development of cell line 1-17, a multipotent clonal human PDL cell line that expresses the embryonic stem cell-related pluripotency genes Oct3/4 and Nanog, as well as the PDL-related molecules periostin and scleraxis. Continuous treatment of cell line 1-17 with bFGF in osteoblastic induction medium inhibited its calcification, with down-regulated expression of FGF-Receptor 1 (FGF-R1), whereas later addition of bFGF potentiated its calcification. Furthermore, bFGF induced calcification of cell line 1-17 when it was co-cultured with osteoblastic cells. These results suggest that cell line 1-17 is a PDL-committed stem cell line and that bFGF exerts dualistic (i.e., promoting and inhibitory) effects on the osteoblastic differentiation of cell line 1-17 based on its differentiation stage.