Perivascular Stem Cells at the Tip of Mouse Incisors Regulate Tissue Regeneration.
Perivascular Stem Cells at the Tip of Mouse Incisors Regulate Tissue Regeneration.
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DOI：
10.1002/jbmr.2717
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发表时间：
2016-03
期刊：
影响因子：
--
通讯作者：
Sharpe PT
中科院分区：
文献类型：
--
作者：
Pang YW;Feng J;Daltoe F;Fatscher R;Gentleman E;Gentleman MM;Sharpe PT
具有间充质干细胞（MSC）特性的细胞作为静止细胞存在于成年牙髓中，会因损伤而被激活。这些类MSC细胞通过刺激自身增殖并分化为成牙本质细胞样细胞来对牙齿损伤作出反应，这些成牙本质细胞样细胞形成牙本质以修复（修复性牙本质）损伤。在不断生长的小鼠切牙中，切牙尖端的组织在进食过程中会因上下牙齿之间的剪切作用而不断受损，这种剪切作用可使切牙尖端自我锐化。我们已经将小鼠切牙尖端作为牙髓MSCs在连续自然修复/再生过程中所起作用的模型进行了研究。我们发现切牙尖端的牙髓由一团无序的矿化组织构成，该组织是由表达成牙本质细胞标记物DSPP的细胞产生的。这些细胞嵌入到快速形成的矿化组织中，然后在动物进食时丢失。四环素标记显示，在切牙长度方向上，新合成的牙本质矿化组织形成过程中出现了预期的标记物掺入，而且在切牙尖端覆盖牙髓腔的区域矿化速度非常快。这种组织类似牙本质，但通过拉曼光谱测定，其矿物质含量明显低于正常牙本质。这种矿物质也比正常牙本质更具结晶性，表明它是由无缺陷的小矿物质颗粒组成的。
为了确定负责矿化组织沉积的细胞的来源，我们通过将NG2ERT2Cre和Nestin Cre小鼠与报告小鼠杂交，对血管周细胞（周细胞）进行了基因标记。在切牙尖端的牙髓中可以看到大量源自周细胞的细胞，其中一些具有细长的、成牙本质细胞样的形状。这些结果表明，在小鼠切牙中，切牙尖端会快速、连续地发生矿化，以将牙髓组织与外界环境隔绝，防止感染。矿物质是由血管周来源的细胞形成的，这些细胞分化为表达DSPP的细胞，并在一个似乎作为连续自然组织再生的过程中产生一种类似牙本质的材料。
Cells with mesenchymal stem cell (MSC) properties are present in adult tooth pulp as quiescent cells that are mobilised by damage. These MSC-like cells respond to tooth damage by stimulating their proliferation and differentiation into odontoblast-like cells that form dentine to repair (reparative dentine) the damage. In the continuously growing mouse incisor, tissue at the incisor tips is continuously being damaged during feeding by the shearing action between the upper and lower teeth that acts to self-sharpen the tips. We have investigated mouse incisor tips as a model for the role of pulp MSCs in a continuous natural repair/regeneration process. We show that the pulp at the tip of the incisor is composed of a disorganised mass of mineralised tissue that is produced by cells expressing the odontoblast cell marker DSPP. These cells become embedded into the mineralised tissue that is rapidly formed and then lost as the animal feeds. Tetracycline labelling revealed the expected incorporation into newly synthesised dentine mineralised tissue formation along the length of the incisor, but also a zone covering the pulp cavity at the tips of the incisors that is mineralised very rapidly. This tissue was dentine-like, but had a significantly lower mineral content than normal dentine as determined by Raman spectroscopy. The mineral was also more crystalline than normal dentine, suggesting that it was composed of small, defect-free mineral particles. To identify the origin of the cells responsible for the deposition of mineralised tissue we genetically labelled perivascular cells (pericytes) by crossing NG2ERT2Cre and Nestin Cre mice with reporter mice. A large number of pericyte-derived cells were visible in the pulp at the incisor tip with some having an elongated, odontoblast-like shape. These results show that in the mouse incisor, rapid, continuous mineralisation occurs at the tip to seal-off the pulp tissue from the external environment to prevent infection. The mineral is formed by perivascular-derived cells that differentiate into cells that express DSPP and produce a dentine-like material in a process that appears to function as continuous natural tissue regeneration.
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影响因子：
0.7
作者：
Lovschall, Henrik;Mitsiadis, Thimios A.;Kjeldsen, Annette L.
通讯作者：
Kjeldsen, Annette L.
影响因子：
1.9
作者：
Bègue-Kirn, C;Ruch, JV;Butler, WT
通讯作者：
Butler, WT
影响因子：
7.8
作者：
Harada, H;Kettunen, P;Jung, H S;Mustonen, T;Wang, Y A;Thesleff, I
通讯作者：
Thesleff, I
DOI：
10.1067/moe.2002.120974
发表时间：
2002-04-01
影响因子：
--
作者：
Murray, PE;Stanley, HR;Smith, AJ
通讯作者：
Smith, AJ
影响因子：
4.8
作者：
Chen, S;Rani, S;MacDougall, M
通讯作者：
MacDougall, M