TNF-alpha promotes an odontoblastic phenotype in dental pulp cells.
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.
Paula-Silva
F W G
FW
Department of Periodontics and Oral Medicine, School of Dentistry, University of Michigan, 1011 N. University Ave., Ann Arbor, MI 48109-1078, USA.
Ghosh
A
A
Silva
L A B
LA
Kapila
Y L
YL
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
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