Therapeutic potential of PPARα agonist in ligature-induced experimental periodontitis.

Ying Chen,Yang Hu

doi:10.1590/1678-7757-2021-0648

Abstract

Inflammation-related immune responses and bone metabolism lead to extensive tooth loss in periodontitis.Objective:This study aims to investigate the effect of peroxisome proliferator-activated receptor (PPAR) alpha agonist anti-inflammatory treatment in vitro and in ligature-induced experimental periodontitis in vivo .Methodology:Splenocytes were isolated from C57BL/6J mice and cultured for 48 hours under the following conditions: control, P. gingivalis lipopolysaccharide (LPS) (1 µg/ml); experimental, LPS (1 µg/ml) + PPARα agonist (fenofibrate) at 1, 10, 50, 100 µM. MRNA and secreted protein levels of TNF-α expression were detected by RT-qPCR and ELISA, respectively. Silk ligatures (7-0) were tied around maxillary second molars of C57BL/6J mice for two weeks. Optimized doses of fenofibrate (50 µM) and vehicle control were injected into the contralateral side of the palatal gingiva on days three, six, and nine. At day 14, bone resorption, osteoclastogenesis, and gingival mRNA expression levels of TNF-α, IL-1β, IL-6, and RANKL/OPG were measured by micro-computed tomography, Tartrate-resistant acid phosphatase (TRAP) staining, and Real-time quantitative PCR, respectively.Results:TNF-α expression in cultured spleen cells were significantly increased in the presence of LPS, when compared with the control group, and significantly reduced by fenofibrate treatment in a dose-dependent manner from 1-100 µM (p<0.05). Gingival mRNA levels of TNF-α, IL-1β, IL-6, and the ratio of RANKL/OPG, were significantly decreased after injection of fenofibrate, when compared to the control side (p<0.05). Periodontal bone loss and TRAP positive cell formation were significantly decreased on the side with an injection of fenofibrate, as compared to the control side (p<0.05).Conclusions:An anti-inflammatory treatment, PPARα agonist, inhibited inflammation and periodontal bone loss in ligature-induced experimental periodontitis.

Highlights

This study aims to investigate the effect of peroxisome proliferator-activated receptor (PPAR) alpha agonist anti-inflammatory treatment in vitro and in ligature-induced experimental periodontitis in vivo
Effects of PPARα agonist treatment on TNF-α mRNA level of splenocytes induced by LPS
Our study showed that mice with ligature-induced periodontitis exhibited a significant upregulation of IL-1, IL6, and TNF-α expression, which were downregulated by the administration of fenofibrate, compared with control experimental periodontal disease mice (Figure 6)

Summary

Introduction

The periodontium consists of the gingiva, periodontal ligament, cementum, and the alveolar bone proper. These teeth-surrounding tissues support teeth in the maxillary and mandibular bones and maintain teeth functioning.[1]. Periodontal disease is a progressive inflammatory process affecting teeth-surrounding tissues, destroying bone-supporting tissues, inducing bone resorption, and constituting the leading cause of bone loss in teeth.[2]. A various range of inflammatory cytokines and signaling pathways have been shown to mediate the pathological process of periodontitis.[2]. Inflammatory factors, tumor necrosis factor-alpha (TNF-α), and interleukin-I (IL-1) play the causative pathological roles of destroying periodontal tissues.[3]. IL-1 induces adhesion molecules and a number of inflammatory factors to attack the periodontal tissues, resulting in the loss of connective tissue attachment, osteoclast formation, bone resorption, and loss of alveolar bone.[5]. Antagonizing IL-1 and TNF-α in experimental periodontitis has shown the beneficial effects of inhibiting the activity of pro-inflammatory cytokines and the further spread of the inflammation in the periodontal tissues.[7]

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