Characteristic phenotype of immortalized periodontal cells isolated from a Marfan syndrome type I patient
Characteristic phenotype of immortalized periodontal cells isolated from a Marfan syndrome type I patient
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DOI：
10.1007/s00441-007-0528-x
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发表时间：
2008-02-01
影响因子：
3.6
通讯作者：
Suda, Naoto
中科院分区：
文献类型：
--
作者：
Shiga, Momotoshi;Saito, Masahiro;Suda, Naoto
牙周韧带（PDL）位于牙根和牙槽骨之间，支持牙齿，由胶原蛋白和弹性系统纤维组成。马凡综合征I型（MFS1, MIM #154700）是由编码纤维蛋白1的FBN1突变引起的，纤维蛋白1是弹性系统纤维的主要微纤维蛋白。MFS1的特征是身材高大，主动脉瓣/二尖瓣脱垂和晶状体异位，偶尔伴有严重的牙周炎。由于对PDL弹性系统纤维的生物学功能和MFS1牙周炎的发病机制知之甚少，我们从一名患有FBN1钙结合表皮生长因子样结构域杂合错义突变的MFS1患者中分离出PDL细胞。通过转导携带人类Polycomb蛋白、Bmi-1和人类端粒酶逆转录酶基因的逆转录病毒，使分离的PDL细胞永生化。来自MFS1患者的永活PDL细胞（称为M-HPL1）和健康志愿者的永活PDL细胞（称为HPDL2）均表达各种PDL相关基因。M-HPL1和HPDL2在羟基磷灰石颗粒上的生长和附着具有可比性。然而，当M-HPL1与羟基磷灰石颗粒一起移植到免疫缺陷小鼠体内时，发现细胞排列紊乱，微纤维组装不规则。转化生长因子- β (tgf - β)信号的激活被认为是导致MFS1肺和心血管异常的发病机制。有趣的是，M-HPL1比HPDL2表现出更高水平的活化tgf - β。因此，M-HPL1是阐明弹性系统纤维在PDL中的生物学作用和MFS1牙周炎发病机制的有力工具。我们的研究结果还表明，FBN1调节pdl中的细胞排列和微纤维组装。
The periodontal ligament (PDL) is situated between the tooth root and alveolar bone, thereby supporting the tooth, and is composed of collagen and elastic system fibers. Marfan syndrome type I (MFS1, MIM #154700) is caused by mutations in FBN1 encoding fibrillin-1, which is a major microfibrillar protein of elastic system fibers. MFS1 is characterized by tall stature, aortic/mitral valve prolapse, and ectopia lentis and is occasionally accompanied by severe periodontitis. Since little is known about the biological functions of elastic system fibers in PDLs and the pathogenesis of the periodontitis in MFS1, PDL cells were isolated from an MFS1 patient with a heterozygous missense mutation in a calcium-binding epidermal-growth-factor-like domain of FBN1. Isolated PDL cells were immortalized by transducing a retrovirus carrying genes for the human Polycomb group protein, Bmi-1, and human telomerase reverse transcriptase. Immortalized PDL cells from the MFS1 patient (termed M-HPL1) and those of a healthy volunteer (termed HPDL2) both expressed various PDL-related genes. The growth and attachment of M-HPL1 and HPDL2 to hydroxyapatite particles were comparable. However, when M-HPL1 were transplanted with hydroxyapatite particles into immunodeficient mice, disorganized cell alignment and irregular microfibril assembly were noted. The activation of the signaling of transforming grwoth factor-beta (TGF-beta) is thought to cause the pathogenesis for lung and cardiovascular abnormalities in MFS1. Interestingly, M-HPL1 shows a higher level of activated TGF-beta than HPDL2. Thus, M-HPL1 represent a powerful tool for clarifying the biological roles of elastic system fibers in PDL and the pathogenesis of periodontitis in MFS1. Our findings also suggest that FBN1 regulates cell alignment and microfibril assembly in PDLs.