Simvastatin increases cell viability and suppresses the expression of cytokines and vascular endothelial growth factor in inflamed human dental pulp stem cells in vitro

BACKGROUND: In recent years, simvastatin has been demonstrated to be capable of inducing odontogenic differentiation in human dental pulp stem cells (DPSCs), which makes it a promising source for endodontic treatment in pulpitis. However, a comprehensive understanding of how simvastatin affects the behavior of DPSCs and its potential in pulpitis is still lacking. OBJECTIVES: In this study, we investigated the effects of simvastatin on the viability of inflamed DPSCs. The expression of cytokines and vascular endothelial growth factor (VEGF) was also studied in response to simvastatin treatment. MATERIAL AND METHODS: We characterized the cell viability, inflammatory reactions and the production of VEGF in inflamed DPSCs, induced by lipopolysaccharides (LPS). The methylthiazolyldiphenyl-tetrazolium bromide (MTT) assay, cell cycle, apoptosis analysis, quantitative reverse transcription polymerase chain reaction (RT-PCR), enzyme-linked immunosorbent assay (ELISA), and western blot analyses were performed. RESULTS: We observed that a low dosage of simvastatin accelerated cell proliferation , whereas its high dosage (>15 μg/mL) suppressed propagation. A simvastatin dose of 8 μg/mL was sufficient to promote cell growth and cell cycle progression in DPSCs treated with LPS. Meanwhile, simvastatin induced apoptosis. The expression of multiple cytokines, including interleukins (IL)-1, IL-4 and IL-1β, and especially interferon-gamma (IFN-γ) and tumor necrosis factor-alpha (TNF-α), was significantly suppressed. Moreover, the protein secretion and mRNA transcription of VEGF was observed to be markedly inhibited by simvastatin by inactivating mitogen-activated protein kinase (MAPK) signaling. CONCLUSIONS: Taken together, these results suggested that simvastatin might be a potent ingredient to enhance cell proliferation, alleviate inflammation response and attune vasculogenesis in pulpitis.