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The Effect of TNF- alpha On The Odontogenic Potential Of Human Dental Stem Cells

Abstract

Tumor necrosis factor- alpha (TNF- α) is a major inflammatory cytokine that stimulates apoptotic signaling pathway and activates the transcription factor nuclear factor kappa B (NF- κB). Its contribution of apoptosis and rate of differentiation in regulating osteoblasts remains controversial. Recently, human mesenchymal stem cells were demonstrated in dental tissues. Human dental stem cells are also multipotent and can be induced to differentiate into different cell lineages. These cells are definitely a key part of achieving the promise of tissue and bone regeneration, along with bone marrow stem cells. In this research study, we wanted to see the effect of TNF- α on odontogenic differentiation of dental stem cells. We treated two different dental stem cell (DSCs) lines - dental pulp stem cells (DPSCs), and apical papilla (SCAPs) with 1ng/mL of TNF- α in different time points. Within 7 days, we could see an early alkaline phosphatase (ALP) expression and activity. In addition, ALP expression and activity were higher with treatment at 1ng/ml. Enhanced matrix mineralization was also observed with Alizarin Red Staining (ARS) after 14 days, and the mineralization was stronger with lower TNF- α concentration treatments. Furthermore, we investigated the effect of TNF-α on transcription factors, RUNX2 and OSX, two critical factors in osteogenic and odontogenic differentiation. The results showed that TNF- α induced the RUNX2 expression in both dental stem cells at different time points (4 hours and 24 hours). However, we observed a decrease in the expression of OSX. In this study, we demonstrated that TNF- α (at a lower concentration) could enhance odontogenic differentiation in dental stem cells. The amount of exposure of TNF- α might be a critical factor in determining its effects on odontoblast lineage commitment of dental stem cells.

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