Simvastatin, Cholesterol-lowering Drug, as a New Therapeutic Agent for Periodontal Regeneration

Abstract

In 1999, Mundy et al. has indicated that statins, drugs widely used for lowering serum cholesterol, stimulate bone formation in rodents and increase bone morphogenetic protein (BMP)-2 expression in vitro. However, the other growth factors except for BMP-2 and the effects of simvastatin, one of statins, on periodontal tissues have not been shown yet. The purpose of this study was to investigate the possibility of statins as a new effective agent for periodontal regeneration using luciferase reporter gene assay and reverse transcription- polymerase chain reaction (RT-PCR), and the alkaline phosphatase (ALP) activity in human periodontal ligament (HPDL) cells. The results showed that simvastatin induced not only BMP-2 but also transforming growth factor-β1 (TGF-β1) in HPDL cells and human osteoblastic cells (NHOst). To examine whether the TGF-â1 activity was related with productions of the cholesterol biosynthetic pathway, HPDL cells were treated with simvastatin in the presence or absence of mevalonic acid. The TGF-β1 induction was caused by the inhibition of cholesterol biosynthetic pathway. The differentiation study showed that TGF-β1 increased the ALP activity, but BMP-2 decreased the ALP activity in HPDL cells, even in the presence of TGF-β1. The effect of simvastatin is similar to that for BMP-2 with TGF-β1. The above in vitro findings suggest that simvastatin may be effective for periodontal regeneration as new therapeutic agents to induce the regenerative factors such as TGF-β1 and BMP-2.