Identification of novel candidate genes involved in mineralization of dental enamel by genome-wide transcript profiling

LacruzR.S.; SmithC.E.; BringasP.ChenY.-B.SmithS.M.SneadM.L.KurtzI.HaciaJ.G.HubbardM.J.PaineM.L.

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Identification of novel candidate genes involved in mineralization of dental enamel by genome-wide transcript profiling

机译：新型候选基因的识别在牙釉质矿化的全基因组记录分析

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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.

机译：基因调节脊椎动物生物矿化是知之甚少。搪瓷,最高度矿化组织哺乳动物,不同于其他钙化系统形成细胞(造釉细胞)所缺乏的很大程度上降低和改造活动再吸收最初的细胞外基质。矿化要求造釉细胞经历深刻的功能开关matrix-secreting成熟(钙运输、蛋白质吸收)的角色矿化过程。阶段,细胞外的pH值显著降低,将高要求造釉细胞调节酸性环境中呈现增长羟磷灰石晶体。事件驱动釉质矿化,我们进行了全基因组转录分析的发展从老鼠门齿和釉质器突出显示超过300个差异表达的基因在成熟。分析,我们确定了组织的maturation-associated基因的功能与关键成矿过程包括有关调节pH值、钙处理和矩阵营业额。分析表明,溶质载体(SLC)基因家族成员差异在成熟过程中,包括小说的蛋白质Slc24a4参与钙处理以及其他蛋白相似的函数(Stim1)。提供的第一个全球概览搪瓷所需细胞机制成熟,这项研究提供了一个强大改善的基本理解的基础生物矿化及其实际应用在医疗保健。

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《Journal of Cellular Physiology》 |2012年第5期|2264-2275|共12页
作者
LacruzR.S.; SmithC.E.; BringasP.ChenY.-B.SmithS.M.SneadM.L.KurtzI.HaciaJ.G.HubbardM.J.PaineM.L.;
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作者单位

Departments of Paediatrics and Pharmacology, University of Melbourne, Melbourne, VIC, Australia;

Department of Biochemistry and Molecular Biology, Broad Center for Regenerative Medicine and Stem;

Facility for Electron Microscopy Research, Department of Anatomy and Cell Biology, McGillCenter for Craniofacial Molecular Biology, Herman Ostrow School of Dentistry, University ofDivision of Nephrology, David Geffen School of Medicine at UCLA, Los Angeles, CA, United StatesNorris Medical Library, University of Southern California, Los Angeles, CA, United States;

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正文语种英语
中图分类细胞生物学;
关键词
biomineralization; Dental Enamel; MineralizationEnamel OrganMaturationAmeloblasts;

机译：生物矿化;牙科搪瓷;MineralizationEnamelOrganMaturationAmeloblasts;

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Identification of novel candidate genes involved in mineralization of dental enamel by genome-wide transcript profiling

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