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Effects of Calcitonin Gene-related Peptide on Dental Pulp Stem Cell Viability,Proliferation, and Differentiation
Institution:1. Department of Restorative Dentistry and Biomaterials Sciences, Harvard School of Dental Medicine, Boston, Massachusetts;2. Department of Endodontics, New York University College of Dentistry, New York, New York;1. Department of Conservative Dentistry and Endodontics, Thai Moogambigai Dental College and Hospital, Dr. MGR Educational and Research Institute, Chennai, India;2. Dental Research Institute, Faculty of Dentistry, University of Toronto, Toronto, Ontario, Canada;3. Department of Dentistry, Mount Sinai Hospital, Sinai Health System, Toronto, Ontario, Canada;1. Department of Restorative, Preventive and Pediatric Dentistry, School of Dental Medicine, University of Bern, Bern, Switzerland;2. Department of Periodontology and Operative Dentistry, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany;3. Department for BioMedical Research, University of Bern, Bern, Switzerland;4. Reconstructive Dentistry and Gerodontology, School of Dental Medicine, University of Bern, Bern, Switzerland;6. Division of Preventive Dentistry, Periodontology, and Cariology, University of Zürich Center of Dental Medicine Zürich, Zurich, Switzerland;1. Konya Research and Training Hospital, Konya, Turkey;2. Research Center of Dental Faculty, Hacettepe University, Ankara, Turkey;3. Department of Periodontology, Selcuk University, Konya, Turkey;4. Department of Endodontics, Selcuk University, Konya, Turkey
Abstract:IntroductionPulpitis is an inflammation of dental pulp caused by bacterial proliferation near or within pulpal tissues. In advanced stages, when the inflammation is associated with pulp necrosis, pulp preservation is dependent on dental pulp stem cells (DPSCs) that can differentiate into odontoblastlike cells and produce reparative dentin. In this study, we evaluated the influence of sensory neurons through calcitonin gene-related peptide (CGRP) on DPSC viability and proliferation and the ability of DPSCs to differentiate into mineralizing cells.MethodsCommercially available DPSCs were treated with varying doses of CGRP, and metabolic activity, viability, proliferation, and cell death were evaluated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assays, trypan blue staining, 5-bromo-2'-deoxyuridine cell proliferation assay, and caspase-3 staining, respectively. DPSC differentiation was assessed with alizarin red staining and by quantifying messenger RNA expression of odontoblast makers.ResultsCGRP induced a dose-dependent decrease of DPSC metabolic activity that was prevented by the CGRP receptor antagonist CGRP 8-37. The decrease in the proportion of live cells induced by CGRP is associated with a decrease of cell proliferation but not with caspase-3–dependent apoptosis. Interestingly, dexamethasone-induced DPSC differentiation into mineralizing cells was neither inhibited nor enhanced by CGRP treatment.ConclusionsThe neuropeptide CGRP has an inhibitory effect on DPSC proliferation but does not enhance or inhibit the differentiation of DPSCs into mineralizing cells. This suggests that CGRP might negatively influence the ability of DPSCs to contribute to regenerative or tissue repair processes.
Keywords:Calcitonin gene-related peptide  cell differentiation  dental pulp stem cells  neuropeptide  pulp biology
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