Gene expression profiling of pulpal tissue reveals the molecular complexity of dental caries
Gene expression profiling of pulpal tissue reveals the molecular complexity of dental caries
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DOI：
10.1016/j.bbadis.2005.03.007
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发表时间：
2005-09-25
影响因子：
6.2
通讯作者：
Cooper, PR
中科院分区：
文献类型：
--
作者：
McLachlan, JL;Smith, AJ;Cooper, PR
高通量表征龋损下牙髓组织的分子反应可能有助于改进未来的诊断和治疗。为了确定与这一过程相关的基因，使用从健康和龋齿的牙髓组织中提取的总RNA，筛选了包含类似15,000个人类序列的寡核苷酸微阵列。数据分析确定了445个表达水平差异2倍或更大的基因，其中85个在健康中表达更丰富，360个在疾病中表达更丰富。随后的基因本体论分组确定了在龋齿过程中可能被激活或下调的各种过程和功能。通过实时和半定量PCR相结合的方法对选定的基因进行验证，确认牙本质基质蛋白-1(DMP-1)、Slit2、周期-2(PER2)、周期-3(PER3)、骨粘着蛋白、Glypcan-3、中期因子、激活素受体相互作用蛋白-1(AIPI)、骨粘着素和生长激素受体(GHR)下调，肾上腺髓质素(ADM)、白细胞介素11(IL-11)、骨唾液蛋白(BSP)、基质GLA蛋白(MGP)、内皮细胞生长因子-1(ECGF1)上调抑制素βA和类粘蛋白1(ORM1)，在病变牙髓中。对一组健康和龋齿牙髓组织以及免疫系统细胞中ADM和DMP-1的实时PCR分析突显了龋病的异质性，并表明在细菌产品激活的中性粒细胞中ADM的表达增加。相比之下，DMP-1主要由健康牙髓组织固有的细胞表达。这项研究极大地扩展了我们对牙齿组织疾病的分子知识，并确定了以前与这一过程无关的基因的参与。(C)2005 Elsevier B.V.保留所有权利。
High-throughput characterisation of the molecular response of pulpal tissue under carious lesions may contribute to improved future diagnosis and treatment. To identify genes associated with this process, oligonucleotide microarrays containing similar to 15,000 human sequences were screened using pooled total RNA isolated from pulpal tissue from both healthy and carious teeth. Data analysis identified 445 genes with 2-fold or greater difference in expression level, with 85 more abundant in health and 360 more abundant in disease. Subsequent gene ontological grouping identified a variety of processes and functions potentially activated or down-modulated during caries. Validation of microarray results was obtained by a combination of real-time and semi-quantitative PCR for selected genes, confirming down-regulation of Dentin Matrix Protein-1 (DMP-1), SLIT2, Period-2 (PER2), Period-3 (PER3), osteoadherin, Glypican-3, Midkine, activin receptor interacting protein-1 (AIPI), osteoadherin and growth hormone receptor (GHR), and up-regulation of Adrenomedullin (ADM), Interleukin-11 (IL-11), Bone sialoprotein (BSP), matrix Gla protein (MGP), endothelial cell growth factor-1 (ECGF1), inhibin beta A and orosomucoid-1 (ORM1), in diseased pulp. Real-time PCR analyses of ADM and DMP-1 in a panel of healthy and carious pulpal tissue and also in immune system cells highlighted the heterogeneity of caries and indicated increased expression of ADM in neutrophils activated by bacterial products. In contrast, DMP-1 was predominantly expressed by cells native to healthy pulpal tissue. This study has greatly extended our molecular knowledge of dental tissue disease and identified involvement of genes previously unassociated with this process. (c) 2005 Elsevier B.V. All rights reserved.