Effect Of Simvastatin On The Expression Of MMP-1in Rats With Periodontitis During Retention Stage After Tooth Movement

Objective: Using established the models of rats with experimental periodontitisin the retention stage after the orthodontic tooth movement to simulate the commonconditions in clinical retention of periodontitis patients after the orthodontic toothmovement, the effect of simvastatin on the remodeling of periodontal tissue andalveolar bone in rats with the periodontitis in the retention stage after orthodontictooth movement was observed with systemic administration of different drugs andexamining histological changes and the expression level of MMP-1in the tissue inthe mesial and distal side of moved teeth at various time points. The feasibility ofusing anti-inflammatory drugs in clinical to promote the stabilization of theorthodontic teeth in retention stage is explored.Methods: After established periodontitis model, fifty-five4-week-old maleWistar rats were randomly divided into11groups and each group had5rats.(1) Oneblank control group: Experimental tooth movement was performed on rats withperiodontitis. The maxillary first molars were mesially moved for21days under theanchorage of anterior teeth.(2) Five experimental control groups: The toothmovement was performed the same as in the blank control group but retainers wereplaced on left side for1,3,7,14,21days. During the retention stage, normal salinewas injected intraperitoneally every day. The first injection was done on the one daybefore retention.(3) Five simvastatin groups: Animals were treated in the same wayas in experimental control groups but were administered simvastatin solution insteadof normal saline. At the end of the retention, all rats were euthanized throughtranscardial perfusion and mesiodistal pathological sections were cut and stainedwith HE and immunohistochemistry so that the histological changes and MMP-1expression in periodontal tissues of moved teeth were examined.Innovations:1. Simvastatin belongs to statins, and as the classic and effective lipid-lowering drug it was widely used in the treatment of hyperlipidemia in theclinical[1~3]. In recent years, with the developments in the basic research on statins,they were also showed some new applications in clinical. For example, they can playthe roles in improving endothelial function, anti-inflammatory, inhibiting plateletfunction, inhibiting thrombosis, antioxidant and stabilizing the atheroscleroticplaques[4]. In addition, the effects of simvastatin on bone metabolism and its actionmechanism has also become a hot spot in studies[5~13]. Though a growing number ofdental researchers have begun to focus on the effects of simvastatin on the boneremodeling, there is little research on the effect of simvastatin anti-inflammatoryfunction on the bone remodeling.2. After orthodontic tooth movements, periodontaltissue remodeling includes alteration of alveolar bone and periodontal ligamentreconstruction, but there is less research on the ligament reconstruction afterorthodontic tooth movement in current experimental studies.3. MMP-1as interstitialcollagen fibers enzyme plays an important role in the remodeling of periodontalmembrane[14]. The current studies on MMP-1are mainly focused on the relationshipbetween MMP-1and periodontitis[15~17], the relationship between MMP-1andhistological changes in tooth movement[18、19], and the effect of anti-inflammatorydrugs on the expression level of MMP-1[20、21]. However, there is still little study onthe relationship between MMP-1and histological changes during retention stageafter tooth movement. This study examines the effects of simvastatin on theexpression of MMP-1in rats with periodontitis in the retention stage afterorthodontic tooth movement and demonstrates some innovation.4. The retentionafter orthodontic tooth movement in patients with periodontitis remains difficultwork for orthodontists. This is also a problem all orthodontists confront. To findsome method, which is both convenient and efficient and can be accepted by themajority of patients, has become the pursuit of orthodontists. In order to explore thisproblem, the present study establishes the animal models, observes and discusses theeffects of simvastatin on periodontal tissue remodeling in various time points usingsystemic administration and MMP-1as an observed indicator, and providesexperimental data for anti-inflammatory drugs to be ultimately applicable in the orthodontic clinic.Results: During the retention stage，the expression of MMP-1was increasing inthe mesial side until the7days, and then decreasing. In the distal of non-retainer side,the expression changed insignificantly in the first few days both in the simvastatingroups and the experimental control groups but after7days the expression started toincrease, and then to decrease from14days. In the distal of retained side, both thetwo groups showed decreasing trend but at the same time point, the expression wassignificantly lower in the simvastatin groups than in the control groups.Conclusions:1. On the level of histological structure, simvastatin can promotethe remodeling of periodontal tissue of moved teeth, facilitate tissue regenerationand help to stabilize the teeth in the new position.2. On the cellular and molecularlevel, simvastatin can reduce the expression of MMP-1and inflammation reaction inperiodontal membrane, and inhibit the degradation of collagen so as to promote theremodeling of periodontal tissue.3. The present study demonstrates that simvastatincan promote periodontal tissue remodeling of orthodontic tooth in rats withperiodontitis in retention stage and shorten retention time.