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Comparative Study
. 2014 Mar;93(3):294-9.
doi: 10.1177/0022034513516980. Epub 2013 Dec 18.

Simvastatin inhibits LPS-induced alveolar bone loss during metabolic syndrome

J Jin  1 , E R Machado, H Yu, X Zhang, Z Lu, Y Li, M F Lopes-Virella, K L Kirkwood, Y Huang
Affiliations
Comparative Study

Simvastatin inhibits LPS-induced alveolar bone loss during metabolic syndrome

J Jin et al. J Dent Res. 2014 Mar.

Abstract

Studies in recent years have shown a positive relationship between metabolic syndrome (MS) and periodontal disease (PD). Given that patients with MS take statins to reduce cholesterol, and statins also have anti-inflammatory effects, it is important to determine if statin intake hinders the progression of MS-associated PD. In this study, PD was induced in Zucker fat rats (ZFRs), an animal model for MS, and in control lean rats by periodontal injection of Aggregatibacter actinomycetemcomitans lipopolysaccharide (LPS), while simvastatin was given to some of the rats via gavage. After 4 wk of treatment, alveolar bone loss was determined by micro-computed tomography. To explore the underlying mechanisms, we determined the effect of simvastatin on tissue inflammation and the expression of molecules involved in osteoclastogenesis. Results showed that while bone loss was increased by LPS in both ZFRs and the control lean rats, it was significantly more in the former than the latter. Simvastatin effectively alleviated bone loss in both ZFRs and the control rats. Results also showed that LPS stimulated leukocyte tissue infiltration and expression of molecules for osteoclastogenesis, but simvastatin significantly modulated the stimulation. This study demonstrated that simvastatin inhibited LPS-induced alveolar bone loss and periodontal tissue inflammation in rats with MS.

Keywords: inflammation obesity; insulin resistance; lipopolysaccharide; periodontal disease; statin.

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Conflict of interest statement

The authors declare no potential conflicts of interest with respect to the authorship and/or publication of this article.

Figures

Figure 1.
Figure 1.
The effects of lipopolysaccharide (LPS) and simvastatin on weight, lipids, insulin, and insulin resistance in the Zucker fat rats (ZFRs) and the control lean rats. The ZFRs and the control lean rats were treated with phosphate-buffered saline (PBS) (n = 7), LPS (n = 7), or LPS plus simvastatin (n = 8) for 4 wk as described in “Materials & Methods”. Before and after the treatments, body weight (A), glucose (B), insulin (C), homeostasis model assessment of insulin resistance (HOMA-IR) (D), total cholesterol (E), triglycerides (F), and free fatty acids (G) were determined. The data are mean ± SD.
Figure 2.
Figure 2.
Simvastatin inhibited lipopolysaccharide (LPS)-induced alveolar bone loss. The Zucker fat rats (ZFRs) and the control lean rats were treated with phosphate-buffered saline (PBS) (n = 7), LPS (n = 7), or LPS plus simvastatin (n = 8) for 4 wk as described in “Materials & Methods”. After treatment, the maxillae were scanned by mCT, and bone volume fractions were quantified. Representative µCT images (A) and bone volume fractions for 6 groups (B) are shown. The bone loss induced by LPS or LPS plus simvastatin is also presented as a percentage of the control (PBS-treated rats) (C). The data are mean ± SD.
Figure 3.
Figure 3.
Simvastatin inhibited lipopolysaccharide (LPS)-induced leukocyte infiltration and alveolar bone resorption. (A) Histological evaluation of leukocyte infiltration and bone resorption in maxillae after treatment with phosphate-buffered saline (PBS), LPS, or LPS plus simvastatin. After the maxillae were examined by mCT as shown in Fig. 2, they were decalcified and sectioned. Tissue sections (7 µm) were stained with hematoxylin and eosin, and photomicrographs on the first molar of rat maxillae were taken at 40x magnification. The selected areas in the images were amplified to 400x and are presented as the insets in the lower right corner. The scale bar for the lower magnification (40x) images represents 50 µm and that for the higher magnification (400x) images represents 250 µm. (B) Quantification of mononuclear cells under the first molar for rats treated with PBS, LPS, or LPS plus simvastatin. The data are mean ± SD.
Figure 4.
Figure 4.
Simvastatin inhibited lipopolysaccharide (LPS)-stimulated receptor activator of nuclear factor kappa-B ligand (RANKL) and colony-stimulating factor (CSF)2 mRNA expression in periodontal tissue. RNA was isolated from periodontal tissue after treatments with vehicle (PBS) (n = 7), LPS (n = 7), or LPS plus simvastatin (n = 8), and real-time polymerase chain-reaction (PCR) was performed to quantify RANKL and CSF2 mRNA expression. The RANKL and CSF2 expression was normalized to GAPDH expression. The data are mean ± SD.
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