Identification of novel candidate genes involved in mineralization of dental enamel by genome-wide transcript profiling.
Identification of novel candidate genes involved in mineralization of dental enamel by genome-wide transcript profiling.
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通过全基因组转录谱分析鉴定参与牙釉质矿化的新候选基因。
DOI：
10.1002/jcp.22965
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发表时间：
2012-05
影响因子：
5.6
通讯作者：
Paine, Michael L.
中科院分区：
文献类型：
--
作者：
Lacruz, Rodrigo S.;Smith, Charles E.;Bringas, Pablo, Jr.;Chen, Yi-Bu;Smith, Susan M.;Snead, Malcolm L.;Kurtz, Ira;Hacia, Joseph G.;Hubbard, Michael J.;Paine, Michael L.
调控脊椎动物生物矿化的基因库尚不清楚。牙釉质是哺乳动物中矿化程度最高的组织，它与其他钙化系统的不同之处在于，牙釉质的形成细胞（成釉细胞）缺乏重塑活性，主要是降解和吸收最初的细胞外基质。牙釉质矿化需要成釉细胞在矿化过程中经历从基质分泌到成熟（钙转运、蛋白质吸收）的深刻功能转换。在成熟阶段，细胞外pH值显著降低，这对成釉细胞调节生长的羟基磷灰石晶体周围的酸性环境提出了很高的要求。为了确定驱动牙釉质矿化的遗传事件，我们对大鼠门牙发育中的牙釉质器官进行了全基因组转录分析，并突出了300多个在成熟过程中差异表达的基因。利用多种生物信息学分析，我们确定了成熟相关基因组，其功能与关键矿化过程相关，包括pH调节、钙处理和基质周转。随后的qPCR和Western blot分析显示，许多溶质载体（SLC）基因家族成员在成熟过程中上调，包括参与钙处理的新蛋白Slc24a4以及其他类似功能的蛋白（Stim1）。通过对牙釉质成熟所需的细胞机制的首次全面概述，本研究为提高对生物矿化的基本理解及其在医疗保健中的实际应用提供了坚实的基础。
The gene repertoire regulating vertebrate biomineralization is poorly understood. Dental enamel, the most highly mineralized tissue in mammals, differs from other calcifying systems in that the formative cells (ameloblasts) lack remodeling activity and largely degrade and resorb the initial extracellular matrix. Enamel mineralization requires that ameloblasts undergo a profound functional switch from matrix-secreting to maturational (calcium transport, protein resorption) roles as mineralization progresses. During the maturation stage, extracellular pH decreases markedly, placing high demands on ameloblasts to regulate acidic environments present around the growing hydroxyapatite crystals. To identify the genetic events driving enamel mineralization, we conducted genome-wide transcript profiling of the developing enamel organ from rat incisors and highlight over 300 genes differentially expressed during maturation. Using multiple bioinformatics analyses, we identified groups of maturation-associated genes whose functions are linked to key mineralization processes including pH regulation, calcium handling and matrix turnover. Subsequent qPCR and Western blot analyses revealed that a number of solute carrier (SLC) gene family members were up-regulated during maturation, including the novel protein Slc24a4 involved in calcium handling as well as other proteins of similar function (Stim1). By providing the first global overview of the cellular machinery required for enamel maturation, this study provide a strong foundation for improving basic understanding of biomineralization and its practical applications in healthcare.
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影响因子：
8.7
作者：
通讯作者：
--
影响因子：
48
作者：
Jovanovic, Marko;Reiter, Lukas;Picotti, Paola;Lange, Vinzenz;Bogan, Erica;Hurschler, Benjamin A.;Blenkiron, Cherie;Lehrbach, Nicolas J.;Ding, Xavier C.;Weiss, Manuel;Schrimpf, Sabine P.;Miska, Eric A.;Grosshans, Helge;Aebersold, Ruedi;Hengartner, Michael O.
通讯作者：
Hengartner, Michael O.
影响因子：
7.6
作者：
Cao H;Wang J;Li X;Florez S;Huang Z;Venugopalan SR;Elangovan S;Skobe Z;Margolis HC;Martin JF;Amendt BA
通讯作者：
Amendt BA
影响因子：
4.5
作者：
Feske, Stefan
通讯作者：
Feske, Stefan
影响因子：
4.8
作者：
Gawenis, LR;Ledoussal, C;Shull, GE
通讯作者：
Shull, GE