Semaphorin 3A induces mesenchymal-stem-like properties in human periodontal ligament cells.

Semaphorin 3A induces mesenchymal-stem-like properties in human periodontal ligament cells.
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DOI:
10.1089/scd.2013.0405
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发表时间:
2014-09
影响因子:
4
通讯作者:
Naohisa Wada;H. Maeda;Daigaku Hasegawa;S. Gronthos;P. Bartold;D. Menicanin;S. Fujii;S. Yoshida;Atsushi Tomokiyo;Satoshi Monnouchi;A. Akamine
Naohisa Wada;H. Maeda;Daigaku Hasegawa;S. Gronthos;P. Bartold;D. Menicanin;S. Fujii;S. Yoshida;Atsushi Tomokiyo;Satoshi Monnouchi;A. Akamine
中科院分区:
医学3区
文献类型:
--
作者:
Naohisa Wada;H. Maeda;Daigaku Hasegawa;S. Gronthos;P. Bartold;D. Menicanin;S. Fujii;S. Yoshida;Atsushi Tomokiyo;Satoshi Monnouchi;A. Akamine

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牙周膜干细胞(PDLSCs)最近被认为是牙周再生治疗的一种新选择。然而,其中一个问题是由于供者之间干细胞潜力的差异,稳定地产生PDLSCs是困难的。在这里,我们发现Semaphorin 3A(Sema3A)可以诱导人牙周膜(PDL)细胞具有间充质干细胞样特性。在牙齿发育过程中,Sema3A在牙囊以及啮齿动物牙齿和牙周组织中的部分成熟PDL组织中特异表达。在多潜能人PDL细胞克隆中,Sema3A的表达水平高于低分化潜能克隆。过表达Sema3A的PDL细胞表现出向功能性成骨细胞和脂肪细胞分化的增强能力。此外,只有在培养开始时才用Sema3A处理PDL细胞促进成骨,而在整个培养过程中Sema3A处理对成骨分化没有影响。最后,Sema3A过表达的PDL细胞上调了胚胎干细胞标志物(NANOG、OCT4和E-cadherin)和间充质干细胞标志物(CD73、CD90、CD105、CD146和CD166)的表达,Sema3A促进了PDL细胞的细胞分裂活性。这些结果提示Sema3A可能具有将PDL细胞转化为间充质干细胞样细胞的功能。
Periodontal ligament stem cells (PDLSCs) have recently been proposed as a novel option in periodontal regenerative therapy. However, one of the issues is the difficulty of stably generating PDLSCs because of the variation of stem cell potential between donors. Here, we show that Semaphorin 3A (Sema3A) can induce mesenchymal-stem-like properties in human periodontal ligament (PDL) cells. Sema3A expression was specifically observed in the dental follicle during tooth development and in parts of mature PDL tissue in rodent tooth and periodontal tissue. Sema3A expression levels were found to be higher in multipotential human PDL cell clones compared with low-differentiation potential clones. Sema3A-overexpressing PDL cells exhibited an enhanced capacity to differentiate into both functional osteoblasts and adipocytes. Moreover, PDL cells treated with Sema3A only at the initiation of culture stimulated osteogenesis, while Sema3A treatment throughout the culture had no effect on osteogenic differentiation. Finally, Sema3A-overexpressing PDL cells upregulated the expression of embryonic stem cell markers (NANOG, OCT4, and E-cadherin) and mesenchymal stem cell markers (CD73, CD90, CD105, CD146, and CD166), and Sema3A promoted cell division activity of PDL cells. These results suggest that Sema3A may possess the function to convert PDL cells into mesenchymal-stem-like cells.