Regulation of reactionary dentin formation by odontoblasts in response to polymicrobial invasion of dentin matrix.
Regulation of reactionary dentin formation by odontoblasts in response to polymicrobial invasion of dentin matrix.
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DOI：
10.1016/j.bone.2011.10.031
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发表时间：
2012-01
期刊：
影响因子：
4.1
通讯作者：
Hunter, Neil
中科院分区：
文献类型：
--
作者：
Charadram, Nattida;Farahani, Ramin M.;Harty, Derek;Rathsam, Catherine;Swain, Michael V.;Hunter, Neil
牙本质的成牙本质细胞合成通过离散但重叠的阶段进行，其特征在于形成图案化的有机基质，随后是重塑和活性矿化。龋齿中牙本质的微生物侵入触发成牙本质细胞的适应性反应，最终形成结构改变的反应性牙本质，其特征在于生物化学和结构修饰，包括减少的管状性。反应性牙本质的胶原蛋白框架的扫描电子显微镜显示了一个根本性的修改，但高度组织化的网状结构所示的分形和孔隙度分析。免疫金标记显示反应性牙本质中牙本质涎蛋白（DSP）密度增加，空间分布规则。DSP在胶原支架上提供了推定的羟基磷灰石成核位点。为了进一步剖析这种改变的牙本质基质的形成，研究了相关的酶机制。提取的牙本质基质的分析表明，基质金属蛋白酶-2（MMP-2）的活性增加的反应区参考生理牙本质。同样，显微解剖的成牙本质细胞层的基因表达分析揭示了MMP-2的上调。金属蛋白酶组织抑制因子-2（TIMP-2）和膜型基质金属蛋白酶1（MT 1-MMP）在龋病中表达上调。其次，调制成牙本质细胞的牙本质酶库解决。在成牙本质细胞层的Toll样受体的表达显着改变，响应细菌入侵。在龋齿中TLR-2和编码相应衔接蛋白MyD 88的基因下调，而编码TLR-4和衔接蛋白TRAM和Mal/TIRAP的基因上调。由细菌产物结合介导的TLR-4信号传导与MMP-2的上调有关。此外，编码TGF-β信号传导途径组分（即SMAD-2和SMAD-4）的基因表达增加可能解释了龋齿中成牙本质细胞胶原蛋白合成增加的原因。这些发现表明，成牙本质细胞对微生物侵入牙本质的根本适应性反应，从而合成改性矿化基质。
Odontoblast synthesis of dentin proceeds through discrete but overlapping phases characterized by formation of a patterned organic matrix followed by remodelling and active mineralization. Microbial invasion of dentin in caries triggers an adaptive response by odontoblasts, culminating in formation of a structurally altered reactionary dentin, marked by biochemical and architectonic modifications including diminished tubularity. Scanning electron microscopy of the collagen framework in reactionary dentin revealed a radically modified yet highly organized meshwork as indicated by fractal and lacunarity analyses. Immuno-gold labelling demonstrated increased density and regular spatial distribution of dentin sialoprotein (DSP) in reactionary dentin. DSP contributes putative hydroxyapatite nucleation sites on the collagen scaffold. To further dissect the formation of this altered dentin matrix, the associated enzymatic machinery was investigated. Analysis of extracted dentin matrix indicated increased activity of matrix metalloproteinase-2 (MMP-2) in the reactionary zone referenced to physiologic dentin. Likewise, gene expression analysis of micro-dissected odontoblast layer revealed up-regulation of MMP-2. Parallel up-regulation of tissue inhibitor of metalloproteinase-2 (TIMP-2) and membrane type 1- matrix metalloproteinase (MT1-MMP) was observed in response to caries. Next, modulation of odontoblastic dentinogenic enzyme repertoire was addressed. In the odontoblast layer expression of Toll-like receptors was markedly altered in response to bacterial invasion. In carious teeth TLR-2 and the gene encoding the corresponding adaptor protein MyD88 were down-regulated whereas genes encoding TLR-4 and adaptor proteins TRAM and Mal/TIRAP were up-regulated. TLR-4 signalling mediated by binding of bacterial products has been linked to up-regulation of MMP-2. Further, increased expression of genes encoding components of the TGF-β signalling pathway, namely SMAD-2 and SMAD-4, may explain the increased synthesis of collagen by odontoblasts in caries. These findings indicate a radical adaptive response of odontoblasts to microbial invasion of dentin with resultant synthesis of modified mineralized matrix.
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DOI：
10.1073/pnas.0638023100
发表时间：
2003-04-01
影响因子：
11.1
作者：
Kawasaki, K;Weiss, KM
通讯作者：
Weiss, KM
影响因子：
1.9
作者：
Baba, O;Qin, CL;Butler, WT
通讯作者：
Butler, WT
影响因子：
6
作者：
Farahani, Ramin M.;Nguyen, Ky-Anh;Hunter, Neil
通讯作者：
Hunter, Neil
影响因子：
7.6
作者：
HOJO, S;KOMATSU, M;YAMADA, T
通讯作者：
YAMADA, T
影响因子：
6.2
作者：
Caldwell, CB;Moran, EL;Bogoch, ER
通讯作者：
Bogoch, ER