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

Authors

  • Rodrigo S. Lacruz,

    Corresponding author
    1. Center for Craniofacial Molecular Biology, Herman Ostrow School of Dentistry, University of Southern California, Los Angeles, California
    • Center for Craniofacial Molecular Biology, Herman Ostrow School of Dentistry, University of Southern California, Los Angeles, CA.
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  • Charles E. Smith,

    1. Facility for Electron Microscopy Research, Department of Anatomy & Cell Biology, McGill University, Montreal, Quebec, Canada
    2. Faculty of Dentistry, McGill University, Montreal, Quebec, Canada
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  • Pablo Bringas Jr,

    1. Center for Craniofacial Molecular Biology, Herman Ostrow School of Dentistry, University of Southern California, Los Angeles, California
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  • Yi-Bu Chen,

    1. Norris Medical Library, University of Southern California, Los Angeles, California
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  • Susan M. Smith,

    1. Center for Craniofacial Molecular Biology, Herman Ostrow School of Dentistry, University of Southern California, Los Angeles, California
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  • Malcolm L. Snead,

    1. Center for Craniofacial Molecular Biology, Herman Ostrow School of Dentistry, University of Southern California, Los Angeles, California
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  • Ira Kurtz,

    1. Division of Nephrology, David Geffen School of Medicine at UCLA, Los Angeles, California
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  • Joseph G. Hacia,

    1. Department of Biochemistry and Molecular Biology, Broad Center for Regenerative Medicine and Stem Cell Research, University of Southern California, Los Angeles, California
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  • Michael J. Hubbard,

    1. Departments of Paediatrics and Pharmacology, University of Melbourne, Victoria, Australia
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  • Michael L. Paine

    Corresponding author
    1. Center for Craniofacial Molecular Biology, Herman Ostrow School of Dentistry, University of Southern California, Los Angeles, California
    • Center for Craniofacial Molecular Biology, Herman Ostrow School of Dentistry, University of Southern California, Los Angeles, CA.
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Abstract

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. J. Cell. Physiol. 227: 2264–2275, 2012. © 2011 Wiley Periodicals, Inc.

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