title: Effects of glial cell line-derived neurotrophic factor on dental pulp cells.
abstract: This study investigated the effects of glial cell line-derived neurotrophic factor (GDNF) on dental pulp cells (DPCs). Cultures of DPCs expressed GDNF as well as its receptors, GFRα1 and RET. Addition of recombinant GDNF to cultures in serum-containing medium did not significantly affect DPC growth; however, GDNF dose-dependently increased viable cell number under serum-free culture conditions. Live/dead, lactate dehydrogenase (LDH), and caspases-3/-7 assays demonstrated that cell death occurred under serum-free conditions, and that GDNF significantly reduced the number of dead cells by inhibiting apoptotic cell death. GDNF also stimulated cell proliferation in serum-free conditions, as assessed by the BrdU incorporation assay. The effect of GDNF was abolished in the presence of inhibitors to GFRα1 and RET suggesting receptor-mediated events. This study also demonstrated that GDNF counteracted TNFα-induced DPC cytotoxicity, suggesting that GDNF may be cytoprotective under disease conditions. In conclusion, our findings indicate that GDNF promotes cell survival and proliferation of DPCs and suggest that GDNF may play a multifunctional role in the regulation of dental pulp homeostasis.
authors.affiliation: Oral Biology, School of Dentistry, College of Medical and Dental Sciences, St Chad's Queensway, University of Birmingham, Birmingham BR 6NN, UK.
authors.forename: Z
authors.initials: Z
authors.lastname: Gale
authors.forename: P R
authors.initials: PR
authors.lastname: Cooper
authors.forename: B A A
authors.initials: BA
authors.lastname: Scheven
mesh_terms: D000818:Animals; D017209:Apoptosis; D049109:Cell Proliferation; D002470:Cell Survival; D002478:Cells, Cultured; D016895:Culture Media, Serum-Free; D003782:Dental Pulp / Q000166:cytology* / Q000378:metabolism; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000096:biosynthesis / Q000502:physiology*; D051097:Glial Cell Line-Derived Neurotrophic Factor Receptors / Q000096:biosynthesis / Q000502:physiology*; D006801:Humans; D008297:Male; D051096:Proto-Oncogene Proteins c-ret / Q000096:biosynthesis / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors
chemical_list: D016895:Culture Media, Serum-Free; C511536:GRFalpha-1 protein, rat; C495041:Gdnf protein, rat; D051100:Glial Cell Line-Derived Neurotrophic Factor; D051097:Glial Cell Line-Derived Neurotrophic Factor Receptors; D014409:Tumor Necrosis Factor-alpha; D051096:Proto-Oncogene Proteins c-ret