Effect Of Simvastatin On Periodontal Regeneration

Periodontal defect has always been one of the most common symptoms in periodontal diseases, and it is the most direct reason for teeth loss in adults. For the past tens of years, it has been found to increase greatly with the improvement of life level and the healthy intention of the patients. What's more, many systematic diseases are also caused by periodontal diseases. So it would make great sense not only in understanding the mechanism of periodontal regeneration, but also in reducing teeth loss resulting from periodontal diseases and the rate of systematic diseases, that we make clear the regulation process of periodontal defect and try to find some bio- or chemical treatment method for periodontal defect. We have the guided tissue regeneration (GTR), gene therapy, and tissue-engineering treatment for periodontal regeneration until now, but all of them have some disadvantages, such as unpredictability, second-hand surgery, high expenditure or immuno-rejection etc, which make great limitations for their usage clinically. So some researchers pay their attentions to finding some cheap, and easy-for-operating chemical medication, which may be possible for clinical use in this field.Simvastatin is traditionally used to lower the cholesterol in peripheral blood for a long time. Recently, it was found to be able to increase the bone mass, bone mineral density and also the osteogenetic gene expression, and had been used to treat osteoporosis for women in menopause. Since the periodontal tissue has the same tissue origin with bone, which is the ectoblast mesenchymal tissue, also because of the positive effect of simvastatin on bone regeneration, we design a series of in vivo and in vitro experiments, trying to find the effect of simvastatin on periodontal regeneration.In the in vivo experiment, the animal models of periodontal defect were first established with 36 Wistar rats, then 10mg/kg.d simvastatin was given gastrically everyday for 7 consevutive days before and after the surgery respectively. Seven days after the surgery, all the animals were sacrificed by perfusion, and after routine dehydration and embedement in wax, the buccal-lingual serial sections were prepared for HE staining and TRAP staining respectively. Then, histological evaluation of periodontal regeneration was carried out with semiquantitative objective indexes. The results showed that the inflammatory cell infiltration in experimental group was much lighter than that in control group, which had significant difference (P﹤0.05). There was also much morefiber collagen in periodontal tissue of experimental group than that in control group(P﹤0.05), which was densely arranged. There was more new alveolar bone formation in experimental group with more osteoblasts (P﹤0.05). The number of osteoclast in control group was 4.36±2.53, with 3.11±2.06 in experimental group, which also had statistical differences (P﹤0.05). So we could say that systematic application of simvastatin could suppress the periodontal inflammation, as well as its resoption, and increase the remodeling of periodontal collagen and alveolar bone, which would make great positive sense for periodontal defect.In the in vitro experiments, we selected three kinds of cells, eg.PDL cells, AOB cells and MG63 cells, which take part in periodontal regeneration, and treat them with different concentrations of simvastatin (10-9M,10-8M,10-7M,10-6M), using medium only as control, trying to find out its effect on cell proliferation, differentiation migration and osteoblastic gene expression. The results showed that①MG63 cells: simvastatin could suppress its cell proliferation, which would be stronger with the time going-on and the increase of simvastatin concentration. Simvastatin could increase the alkaline phosphatase activity and the osteoblastic gene expression in MG63 cells. However, it had suppressing effect on cell migration.②PDL cells: simvastatin had little suppressing effect on cell proliferation. Although, simvastatin dereased the alkaline phosphatase gene expression in PDL cells, it had positive effect on ALP activity and other osteoblastic gene expression.③AOB cells: simvastatin could also suppress the cell proliferation in AOB cells, whose effect would become more obvious with the increase of concentration. But it could greatly increase the ALP activity and osteoblastic gene expression.Combining the results both in vivo and in vitro , we pointed out that simvastatin could suppress local inflammatory resorption and hard tissue resorption in periodontal tissue, as well as the remodeling of periodontal fiber collagen and alveolar bone, when applied systematically. For the cells taking part in periodontal regeneration, simvastatin could suppress their proliferation, which would become stronger with the time and increase of concentrations, while it also had suppressing effect on cell migration. On the other hank, simvastatin could increase the alkaline phosphatase activity, and most osteoblastic genes'expression. In general, simvastatin could suppress periodontal resorption, and increase its regeneration, which means positive effect on periodontal remodeling. The creative work of our research lies in the overall and systematical evaluation of simvatatin on periodontal regeneration for the first time both in vivo and in vitro. What's more, we give some indications of how simvastatin work during this process of remodeling and its mechanism, which would greatly help its clinical application and the following research work.