title: Nuclear translocation of PKCα isoenzyme is involved in neurogenic commitment of human neural crest-derived periodontal ligament stem cells.
abstract: Stem cells isolated from human adult tissue niche represent a promising source for neural differentiation. Human Periodontal Ligament Stem Cells (hPDLSCs) originating from the neural crest are particularly suitable for induction of neural commitment. In this study, under xeno-free culture conditions, in undifferentiated hPDLSCs and in hPDLSCs induced to neuronal differentiation by basic Fibroblast Growth Factor, the level of some neural markers have been analyzed. The hPDLSCs spontaneously express Nestin, a neural progenitor marker. In these cells, the neurogenic process induced to rearrange the cytoskeleton, form neurospheres and express higher levels of Nestin and Tyrosine Hydroxylase, indicating neural induction. Protein Kinase C (PKC) is highly expressed in neural tissue and has a key role in neuronal functions. In particular the Ca(2+) and diacylglycerol-dependent activation of PKCα isozyme is involved in the regulation of neuronal differentiation. Another main component of the pathways controlling neuronal differentiation is the Growth Associated Protein-43 (GAP-43), whose activity is strictly regulated by PKC. The aim of this study is to investigate the role of PKCα/GAP-43 nuclear signal transduction pathway during neuronal commitment of hPDLSCs. During hPDLSCs neurogenic commitment the levels of p-PKC and p-GAP-43 increased both in cytoplasmic and nuclear compartment. PKCα nuclear translocation induced GAP-43 movement to the cytoplasm, where it is known to regulate growth cone dynamics and neuronal differentiation. Moreover, the degree of cytosolic Ca(2+) mobilization appeared to be more pronounced in differentiated hPDLSCs than in undifferentiated cells. This study provides evidences of a new PKCα/GAP-43 nuclear signalling pathway that controls neuronal differentiation in hPDLSCs, leading the way to a potential use of these cells in cell-based therapy in neurodegenerative diseases.
authors.affiliation: Stem Cells and Regenerative Medicine Laboratory, Department of Medical, Oral and Biotechnological Sciences, University "G. d'Annunzio", Chieti-Pescara, via dei Vestini, 31, 66100 Chieti, Italy. Electronic address: oriana.trubiani@unich.it.
authors.forename: Oriana
authors.initials: O
authors.lastname: Trubiani
authors.affiliation: Department of Neuroscience, Imaging and Clinical Sciences - CeSI-MET, University "G. d'Annunzio", Chieti-Pescara, via dei Vestini, 31, 66100 Chieti, Italy.
authors.forename: Simone
authors.initials: S
authors.lastname: Guarnieri
authors.affiliation: Stem Cells and Regenerative Medicine Laboratory, Department of Medical, Oral and Biotechnological Sciences, University "G. d'Annunzio", Chieti-Pescara, via dei Vestini, 31, 66100 Chieti, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Diomede
authors.affiliation: Department of Neuroscience, Imaging and Clinical Sciences - CeSI-MET, University "G. d'Annunzio", Chieti-Pescara, via dei Vestini, 31, 66100 Chieti, Italy.
authors.forename: Maria A
authors.initials: MA
authors.lastname: Mariggiò
authors.affiliation: Stem Cells and Regenerative Medicine Laboratory, Department of Medical, Oral and Biotechnological Sciences, University "G. d'Annunzio", Chieti-Pescara, via dei Vestini, 31, 66100 Chieti, Italy.
authors.forename: Ilaria
authors.initials: I
authors.lastname: Merciaro
authors.affiliation: Department of Neuroscience, Imaging and Clinical Sciences - CeSI-MET, University "G. d'Annunzio", Chieti-Pescara, via dei Vestini, 31, 66100 Chieti, Italy.
authors.forename: Caterina
authors.initials: C
authors.lastname: Morabito
authors.affiliation: Faculté de Médecine, UMR 7365 CNRS-Université de Lorraine, 9, avenue de la Forêt de Haye, 54500 Vandoeuvre-lés-Nancy, France; Cruzeiro do Sul University, Rua Galvão Bueno 868, 01506-000 São Paulo, SP, Brazil.
authors.forename: Marcos F X B
authors.initials: MF
authors.lastname: Cavalcanti
authors.affiliation: Cellular Signalling Laboratory, Department of Biomedical and Neuromotor Sciences, University of Bologna, via Irnerio 48, 40126 Bologna, Italy.
authors.forename: Lucio
authors.initials: L
authors.lastname: Cocco
authors.affiliation: Cellular Signalling Laboratory, Department of Biomedical and Neuromotor Sciences, University of Bologna, via Irnerio 48, 40126 Bologna, Italy.
authors.forename: Giulia
authors.initials: G
authors.lastname: Ramazzotti
mesh_terms: D015415:Biomarkers / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002454:Cell Differentiation; D019070:Cell Lineage; D002467:Cell Nucleus / Q000378:metabolism*; D002478:Cells, Cultured; D019922:GAP-43 Protein / Q000378:metabolism; D006801:Humans; D042541:Intracellular Space / Q000378:metabolism; D007527:Isoenzymes / Q000378:metabolism; D009432:Neural Crest / Q000166:cytology*; D055495:Neurogenesis; D009474:Neurons / Q000166:cytology / Q000201:enzymology; D010513:Periodontal Ligament / Q000166:cytology*; D051571:Protein Kinase C-alpha / Q000378:metabolism*; D021381:Protein Transport; D013234:Stem Cells / Q000166:cytology* / Q000201:enzymology*
chemical_list: D015415:Biomarkers; D019922:GAP-43 Protein; D007527:Isoenzymes; D051571:Protein Kinase C-alpha; D002118:Calcium
keywords: Neurogenic differentiation; Nuclear signalling; Periodontal ligament; Stem cells