Transient Receptor Potential Melastatin Type 7 Channel Is Critical for the Survival of Bone Marrow Derived Mesenchymal Stem Cells
- 1 September 2010
- journal article
- research article
- Published by Mary Ann Liebert Inc in Stem Cells and Development
- Vol. 19 (9), 1393-1403
- https://doi.org/10.1089/scd.2009.0262
Abstract
The transient receptor potential melastatin type 7 channel (TRPM7) is a member of the TRP family of ion channels that is essential for cell proliferation and viability. Mesenchymal stem cells (MSCs) from bone marrow are a potential source for tissue repair due to their ability to differentiate into specialized cells. However, the role of TRPM7 in stem cells is unknown. In this study, we characterized TRPM7 in mouse MSCs using molecular biology, immunocytochemistry, and patch clamp. We also investigated TRPM7 function using a lentiviral vector and specific shRNA to knockdown gene expression. By RT-PCR and immunocytochemistry, we identified TRPM7, but not TRPM6, a close family member with similar function. Electrophysiological recordings during depletion of intracellular Mg2+ or Mg2+-ATP resulted in the development of currents typical for the channel. Furthermore, 2-aminoethoxydiphenyl borate (1 pM–100 μM) inhibited TRPM7 in a concentration-dependent manner. The molecular suppression of TRPM7 significantly decreased MSC proliferation and viability as determined by MTT assay. In addition, TRPM7 gene expression was up-regulated during osteogenesis. These findings demonstrate that TRPM7 is required for MSC survival and perhaps involved in the differentiation process.Keywords
This publication has 45 references indexed in Scilit:
- Deletion of Trpm7 Disrupts Embryonic Development and Thymopoiesis Without Altering Mg 2+ HomeostasisScience, 2008
- Na+‐independent Mg2+ transport sensitive to 2‐aminoethoxydiphenyl borate (2‐APB) in vascular smooth muscle cells: involvement of TRPM‐like channelsJournal of Cellular and Molecular Medicine, 2008
- Magnesium deficiency accelerates cellular senescence in cultured human fibroblastsProceedings of the National Academy of Sciences of the United States of America, 2008
- Importance of melastatin‐like transient receptor potential 7 and cations (magnesium, calcium) in human osteoblast‐like cell proliferationCell Proliferation, 2007
- Functional Transient Receptor Potential Melastatin 7 Channels Are Critical for Human Mast Cell SurvivalThe Journal of Immunology, 2007
- TRP ChannelsAnnual Review of Biochemistry, 2007
- Cell cycle-dependent calcium oscillations in mouse embryonic stem cellsAmerican Journal of Physiology-Cell Physiology, 2007
- Cell cycle-dependent regulation of store-operated ICRAC and Mg2+-nucleotide-regulated MagNuM (TRPM7) currentsCell Calcium, 2007
- Gene expression profiling of human mesenchymal stem cells derived from bone marrow during expansion and osteoblast differentiationBMC Genomics, 2007
- Physical manipulation of calcium oscillations facilitates osteodifferentiation of human mesenchymal stem cellsThe FASEB Journal, 2007