Pulp Progenitor Cell Recruitment is Selectively Guided by a C5a Gradient
Pulp Progenitor Cell Recruitment is Selectively Guided by a C5a Gradient
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DOI：
10.1177/0022034513487377
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发表时间：
2013-06-01
影响因子：
7.6
通讯作者：
About, I.
中科院分区：
文献类型：
--
作者：
Chmilewsky, F.;Jeanneau, C.;About, I.
最近变得明显的是，补体系统的激活也有助于感染/损伤后的组织再生。补体衍生片段C5 a诱导血管修饰并将表达其受体（C5 aR/CD 88）的细胞吸引到感染和组织损伤部位。除了炎性细胞外，各种组织细胞也表达这种受体。我们推测，牙髓祖细胞，暴露于局部补体激活龋齿病变，可能会响应C5 a通过C5 aR。我们的工作旨在评估C5 a诱导牙髓祖细胞迁移的能力，这可能将补体激活与牙本质再生联系起来。第三磨牙牙髓切片的免疫荧光分析显示间充质干细胞标记物STRO-1和C5 aR的血管周围定位。对STRO-1分选的牙髓祖细胞进行RT-PCR，共表达STRO-1和C5 aR，显示高C5 aR mRNA水平。用C5 aR拮抗剂W54011进行的实验表明，C5 a通过C5 aR特异性结合祖细胞，诱导其向C5 a梯度的选择性迁移。由于我们也可以通过免疫组化证实龋齿中C5 b-9的形成，我们的研究结果表明，在局部补体激活后，C5 a诱导牙髓祖细胞迁移，这可能是启动牙本质/牙髓损伤后再生过程的关键。
It recently became evident that activation of the complement system also contributes to tissue regeneration after infection/injury. The complement-derived fragment C5a induces vascular modifications and attracts cells expressing its receptor (C5aR/CD88) to the site of infection and tissue injury. Besides inflammatory cells, various tissue cells express this receptor. We hypothesized that pulp progenitor cells, being exposed to local complement activation in caries lesions, may respond to C5a via the C5aR. Our work aimed at evaluating the ability of C5a to induce pulp progenitor cell migration that may link complement activation to dentin regeneration. Immunofluorescence analysis of third molar pulp sections showed perivascular localization of the mesenchymal stem cell markers STRO-1 and C5aR. RT-PCR on STRO-1-sorted pulp progenitor cells, co-expressing both STRO-1 and C5aR, revealed high C5aR mRNA levels. Experiments with the C5aR antagonist W54011 revealed that C5a specifically bound to progenitor cells via C5aR, inducing their selective migration toward the C5a gradient. Since we could also demonstrate C5b-9 formation by immunohistochemistry in carious teeth, our findings suggest that, upon local complement activation, C5a induces pulp progenitor cell migration, which may be critical in initiating the regenerative process after dentin/pulp injury.