Simvastatin modulates gingival cytokine and MMP production in a rat model of ligature-induced periodontitis

Abstract

PurposeThe aim of this study was to evaluate the effect of simvastatin on the synthesis of cytokines TNF-α and IL-10 and metalloproteinase (MMPs) 2 and 9 in a rat model of ligature-induced periodontitis.Materials and methodsTwenty Wistar rats were used, and a cotton ligature was place in a subgingival position encircling the entire cervix of the first molar of the left (ipsilateral) side of the mandible. The right (contralateral) side of the mandible had no ligature placed and was used as control. After the ligature placement, animals were randomly assigned to two experimental groups (n=10): 1) rats with ligature + vehicle (saline; 10 mL/kg; orally) and 2) rats with ligature + simvastatin (25 mg/kg; orally). After 14 days of treatment, the animals were euthanized by anesthetic overdose and the gingival tissue was removed and homogenized in appropriate buffer. MMP-2 and -9 release as well as the IL-10 and TNF-α levels were detected by enzyme-linked immunosorbent assay. Statistical comparison was performed by unpaired Student’s t-test, with p<0.05 representing significance.ResultsNo differences were observed for TNF-α production between the groups (p>0.05). However, IL-10 was upregulated in simvastatin-treated animals (1.8-fold increase) in comparison with the vehicle-treated group (p<0.05). Simvastatin reduced the gingival levels of MMP-9 (64.3%) in comparison with vehicle-treated samples (p<0.05).ConclusionOral treatment with simvastatin increased the release of IL-10 and reduced the MMP-9 in ligature-induced periodontitis model in rats.

Identification of Genes Differentially Expressed in Simvastatin‐Induced Alveolar Bone Formation

“…MMPs are critical in the degradation of the extracellular matrix composing the connective tissue attachment apparatus to roots, resulting in attachment loss in periodontitis . MMP‐9 in the gingival crevice and surrounding gingiva has been shown to be a primary diagnostic biomarker of human periodontitis, and SIM reduced MMP‐9 in gingiva of a rat ExP model similar to the current study . TNF‐α is a known potent inflammation‐induced osteoclastogenic cytokine .…”

“…(41) MMP-9 in the gingival crevice and surrounding gingiva has been shown to be a primary diagnostic biomarker of human periodontitis, (42) and SIM reduced MMP-9 in gingiva of a rat ExP model similar to the current study. (43) TNF-a is a known potent inflammation-induced osteoclastogenic cytokine. (44) TNF-a strongly promotes inflammatory osteolysis by stimulating activation of macrophages and osteoclast precursors and enhancing expression of osteoclastogenic cytokines.…”

Expression of Concern: MiRNA‐218 regulates osteoclast differentiation and inflammation response in periodontitis rats through Mmp9

“…Because the release of inflammatory factors was also essential for periodontitis occurrence, the effects of miR‐218 and Mmp9 on inflammatory response were assessed in this study. Periodontal tissues showed the increased production of Mmp9 in response to inflammatory factors, and Mmp9 played a vital role in the development and progression of inflammation (Balli et al, ; Mouchrek Junior et al, ; Tsai et al, ). Recent studies have suggested that miRNAs could regulate inflammatory cytokines and contribute to some cancers and inflammatory diseases (Yang et al, ).…”

Thermoresponsive Hydrogel-Based Local Delivery of Simvastatin for the Treatment of Periodontitis

“…As an FDA-approved medication, SIM has a fully established safety profile, which is superior to the BIO used in the previous study . Moreover, in our current in vivo efficacy study, the effective drug dose used was equivalent to 80 μg of SIM per week, which is much lower than the dosing level reported previously. , From the safety perspective, no abnormal body weight change, histological abnormality, or any abnormal behavior was observed during the study, supporting the safety of the formulation.…”