title: TNF-alpha promotes an odontoblastic phenotype in dental pulp cells.
abstract: Dental pulp cells can differentiate toward an odontoblastic phenotype to produce reparative dentin beneath caries lesions. However, the mechanisms involved in pulp cell differentiation under pro-inflammatory stimuli have not been well-explored. Thus, we hypothesized that the pro-inflammatory cytokine tumor necrosis factor-alpha (TNF-alpha) could be a mediator involved in dental pulp cell differentiation toward an odontoblastic phenotype. We observed that TNF-alpha-challenged pulp cells exhibited increased mineralization and early and increased expression of dentin phosphoprotein (DPP), dentin sialoprotein (DSP), dentin matrix protein-1, and osteocalcin during a phase of reduced matrix metalloproteinase (MMP) expression. We investigated whether these events were related and found that p38, a mitogen-activated protein kinase, differentially regulated MMP-1 and DSP/DPP expression and mediated mineralization upon TNF-alpha treatment. These findings indicate that TNF-alpha stimulates differentiation of dental pulp cells toward an odontoblastic phenotype via p38, while negatively regulating MMP-1 expression.
authors.affiliation: Department of Periodontics and Oral Medicine, School of Dentistry, University of Michigan, 1011 N. University Ave., Ann Arbor, MI 48109-1078, USA.
authors.forename: F W G
authors.initials: FW
authors.lastname: Paula-Silva
authors.forename: A
authors.initials: A
authors.lastname: Ghosh
authors.forename: L A B
authors.initials: LA
authors.lastname: Silva
authors.forename: Y L
authors.initials: YL
authors.lastname: Kapila
mesh_terms: D002454:Cell Differentiation / Q000502:physiology*; D003782:Dental Pulp / Q000166:cytology* / Q000378:metabolism; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D006801:Humans; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism; D009804:Odontoblasts / Q000166:cytology*; D010513:Periodontal Ligament / Q000166:cytology* / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism; D012795:Sialoglycoproteins; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism; D014074:Tooth Calcification / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism; D000099311:Dentin Sialophosphoprotein
chemical_list: D016326:Extracellular Matrix Proteins; D020781:Matrix Metalloproteinase 1; D010750:Phosphoproteins; D012795:Sialoglycoproteins; D014409:Tumor Necrosis Factor-alpha; D048051:p38 Mitogen-Activated Protein Kinases; D000099311:Dentin Sialophosphoprotein; C513309:DMP1 protein, human