title: Transient receptor potential melastatin type 7 channel is critical for the survival of bone marrow derived mesenchymal stem cells.
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 Mg(2+) or Mg(2+)-ATP resulted in the development of currents typical for the channel. Furthermore, 2-aminoethoxydiphenyl borate (1 pM-100 microM) 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.
authors.affiliation: Department of Comparative Biomedical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, Louisiana 70803, USA. hcheng@vetmed.lsu.edu
authors.forename: Henrique
authors.initials: H
authors.lastname: Cheng
authors.forename: Ji-Ming
authors.initials: JM
authors.lastname: Feng
authors.forename: Marxa L
authors.initials: ML
authors.lastname: Figueiredo
authors.forename: Hanjie
authors.initials: H
authors.lastname: Zhang
authors.forename: Piper L
authors.initials: PL
authors.lastname: Nelson
authors.forename: Vanessa
authors.initials: V
authors.lastname: Marigo
authors.forename: Andreas
authors.initials: A
authors.lastname: Beck
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D001896:Boron Compounds / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D002478:Cells, Cultured; D006801:Humans; D008297:Male; D059630:Mesenchymal Stem Cells / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010012:Osteogenesis / Q000187:drug effects / Q000235:genetics; D050053:TRPM Cation Channels / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D050051:Transient Receptor Potential Channels / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism / Q000502:physiology
chemical_list: D001896:Boron Compounds; D050053:TRPM Cation Channels; D050051:Transient Receptor Potential Channels; C109986:2-aminoethoxydiphenyl borate; C421903:Trpm7 protein, mouse