Simvastatin Induces Apoptosis in Dental Pulp Cells

The effect of simvastatin, a 3-hydroxy-3-methyglutaryl coenzyme A reductase inhibitor, is still controversial. Low doses of simvastatin were shown to promote odontoblastic differentiation. However, high doses of simvastatin appear to induce apoptosis in several cell types. Objective: The objective of the present study was to investigate the effect of high doses of simvastatin on apoptosis in dental pulp cells in vitro. Materials and methods: Dental pulp cells obtained from 4 patients aged 15-25 years old were exposed to 0.1, 1.0, and 10.0 µM simvastatin for 24, 48, and 72 h. The tetrazolium bromide (MTT) assay was performed to evaluate cell viability. Apoptosis of dental pulp cells was examined by flow cytometry after annexin V/propidium iodide double staining and by analysis of caspase activity. Results: The viability of dental pulp cells was decreased after simvastatin treatment in a dose and time dependent manner. Apoptotic markers such as annexin V labeling and caspase-3 activity as well as the formation of clumped nuclei micronucleus were increased in simvastatin-treated cells. Conclusion: Our data demonstrate that high doses of simvastatin decrease the viability and induce apoptosis of dental pulp cells in vitro. This finding raises the precaution of clinical application of simvastatin in dental pulp treatment. Further studies are required to clarify the molecular mechanism of simvastatin on dental pulp cells.