Transient Receptor Potential Melastatin 4 Channel Controls Calcium Signals and Dental Follicle Stem Cell Differentiation§

Authors

  • Piper Nelson,

    1. Department of Comparative Biomedical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, Louisiana, USA
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  • Tran Doan Ngoc Tran,

    1. Department of Comparative Biomedical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, Louisiana, USA
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  • Hanjie Zhang,

    1. Department of Comparative Biomedical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, Louisiana, USA
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  • Olga Zolochevska,

    1. Department of Pharmacology and Toxicology, University of Texas Medical Branch, Galveston, Texas, USA
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  • Marxa Figueiredo,

    1. Department of Pharmacology and Toxicology, University of Texas Medical Branch, Galveston, Texas, USA
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  • Ji-Ming Feng,

    1. Department of Comparative Biomedical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, Louisiana, USA
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  • Dina L. Gutierrez,

    1. Department of Comparative Biomedical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, Louisiana, USA
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  • Rui Xiao,

    1. Department of Comparative Biomedical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, Louisiana, USA
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  • Shaomian Yao,

    1. Department of Comparative Biomedical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, Louisiana, USA
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  • Arthur Penn,

    1. Department of Comparative Biomedical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, Louisiana, USA
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  • Li-Jun Yang,

    1. Department of Pathology, Immunology and Laboratory Medicine, University of Florida College of Medicine, Gainesville, Florida, USA
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  • Henrique Cheng

    Corresponding author
    1. Department of Comparative Biomedical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, Louisiana, USA
    • Department of Comparative Biomedical Sciences, School of Veterinary Medicine, Louisiana State University, Skip Bertman Drive, Baton Rouge, Louisiana 70803, USA
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    • Telephone: (225)-578-9747; Fax: (225)-578-9895


  • Author contributions: P.N., T.D.N.T., and J-M.F.: collection and/or assembly of data and data analysis and interpretation; H.Z. and D.L.G.: collection and/or assembly of data; O.Z. and L-J.Y.: provision of study material or patients; M.F.: conception and design and provision of study material or patients; R.X. and A.P.: data analysis and interpretation; S.Y.: conception and design and data analysis and interpretation; H.C.: conception and design, collection and/or assembly of data, data analysis and interpretation, and manuscript writing. P.N. and T.D.N.T. contributed equally to this article.

  • Disclosure of potential conflicts of interest is found at the end of this article.

  • §

    First published online in STEM CELLSEXPRESS October 18, 2012.

Abstract

Elevations in the intracellular Ca2+ concentration are a phenomena commonly observed during stem cell differentiation but cease after the process is complete. The transient receptor potential melastatin 4 (TRPM4) is an ion channel that controls Ca2+ signals in excitable and nonexcitable cells. However, its role in stem cells remains unknown. The aim of this study was to characterize TRPM4 in rat dental follicle stem cells (DFSCs) and to determine its impact on Ca2+ signaling and the differentiation process. We identified TRPM4 gene expression in DFSCs, but not TRPM5, a closely related channel with similar function. Perfusion of cells with increasing buffered Ca2+ resulted in a concentration-dependent activation of currents typical for TRPM4, which were also voltage-dependent and had Na+ conductivity. Molecular suppression with shRNA decreased channel activity and cell proliferation during osteogenesis but not adipogenesis. As a result, enhanced mineralization and phosphatase enzyme activity were observed during osteoblast formation, although DFSCs failed to differentiate into adipocytes. Furthermore, the normal agonist-induced first and secondary phases of Ca2+ signals were transformed into a gradual and sustained increase which confirmed the channels' ability to control Ca2+ signaling. Using whole genome microarray analysis, we identified several genes impacted by TRPM4 during DFSC differentiation. These findings suggest an inhibitory role for TRPM4 on osteogenesis while it appears to be required for adipogenesis. The data also provide a potential link between the Ca2+ signaling pattern and gene expression during stem cell differentiation. STEM Cells2013;31:167–177

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