Pivotal Role of Tenascin-W (-N) in Postnatal Incisor Growth and Periodontal Ligament Remodeling.

Pivotal Role of Tenascin-W (-N) in Postnatal Incisor Growth and Periodontal Ligament Remodeling.
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Tenascin-W(-n)在产后切牙生长和牙周韧带重塑中的关键作用。

DOI:
10.3389/fimmu.2020.608223
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发表时间:
2020
影响因子:
7.3
通讯作者:
Koch M
Koch M
中科院分区:
医学2区
文献类型:
--
作者:
Imhof T;Balic A;Heilig J;Chiquet-Ehrismann R;Chiquet M;Niehoff A;Brachvogel B;Thesleff I;Koch M

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不断生长的小鼠门牙为研究干细胞调节和器官更新提供了一个有趣的模型。在门牙中,上皮干细胞和间充质干细胞保证了牙齿的终生生长。上皮干细胞驻留在一个被称为颈环的缝隙中。间充质干细胞位于邻近的顶端神经血管束和神经丛中。到目前为止,人们对控制门牙干细胞更新和引导的细胞外信号知之甚少。细胞外基质蛋白Tenascin-W,也称为Tenascin-N(TNN),表达于牙髓间充质和切牙的牙周韧带中,并与3型胶原纤维密切相关。在这里,我们首次报道了Tenascin-W/TNN缺陷小鼠的表型,在C57BL/6N背景下,这些小鼠的体重和寿命都有所下降。我们发现生长中的啮齿动物门牙的牙槽骨和牙周韧带有主要的缺陷,而磨牙没有受到影响。门牙周围的牙槽骨被致密的疤痕状结缔组织取代,新形成的神经纤维丰富,可能导致牙周疼痛、食物摄入量减少和体重减轻。使用软食物减少切牙的机械负荷部分挽救了表型。原位杂交和Gli1报告鼠实验显示,切牙间充质干细胞隔室中的Hedgehog信号减少,这协调了间充质干细胞生态位的发展。这些结果表明,小鼠TnN缺乏影响牙周改建,增加神经纤维分支。通过牙周疼痛,食物摄入量减少,门牙更新和神经血管声波刺猬分泌率降低。综上所述,Tenascin-W/TnN在快速牙周组织改建中起主要作用,在机械感觉中起次要作用。
The continuously growing mouse incisor provides a fascinating model for studying stem cell regulation and organ renewal. In the incisor, epithelial and mesenchymal stem cells assure lifelong tooth growth. The epithelial stem cells reside in a niche known as the cervical loop. Mesenchymal stem cells are located in the nearby apical neurovascular bundle and in the neural plexus. So far, little is known about extracellular cues that are controlling incisor stem cell renewal and guidance. The extracellular matrix protein tenascin-W, also known as tenascin-N (TNN), is expressed in the mesenchyme of the pulp and of the periodontal ligament of the incisor, and is closely associated with collagen 3 fibers. Here, we report for the first time the phenotype of tenascin-W/TNN deficient mice, which in a C57BL/6N background exhibit a reduced body weight and lifespan. We found major defects in the alveolar bone and periodontal ligament of the growing rodent incisors, whereas molars were not affected. The alveolar bone around the incisor was replaced by a dense scar-like connective tissue, enriched with newly formed nerve fibers likely leading to periodontal pain, less food intake and reduced body weight. Using soft food to reduce mechanical load on the incisor partially rescued the phenotype. In situ hybridization and Gli1 reporter mouse experiments revealed decreased hedgehog signaling in the incisor mesenchymal stem cell compartment, which coordinates the development of mesenchymal stem cell niche. These results indicate that TNN deficiency in mice affects periodontal remodeling and increases nerve fiber branching. Through periodontal pain the food intake is reduced and the incisor renewal and the neurovascular sonic hedgehog secretion rate are reduced. In conclusion, tenascin-W/TNN seems to have a primary function in rapid periodontal tissue remodeling and a secondary function in mechanosensation.
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