Application of Ligature-Induced Periodontitis in Mice to Explore the Molecular Mechanism of Periodontal Disease

Peiya Lin,Akira Aoki,Hiromi Niimi,Tsuyoshi Shimohira,Sayaka Katagiri,Anhao Liu,Yosuke Tsuchiya,Keiji Komatsu,Takahiko Shiba,Yujin Ohsugi,Takanori Iwata

doi:10.3390/ijms22168900

Abstract

Periodontitis is an inflammatory disease characterized by the destruction of the periodontium. In the last decade, a new murine model of periodontitis has been widely used to simulate alveolar bone resorption and periodontal soft tissue destruction by ligation. Typically, 3-0 to 9-0 silks are selected for ligation around the molars in mice, and significant bone loss and inflammatory infiltration are observed within a week. The ligature-maintained period can vary according to specific aims. We reviewed the findings on the interaction of systemic diseases with periodontitis, periodontal tissue destruction, the immunological and bacteriological responses, and new treatments. In these studies, the activation of osteoclasts, upregulation of pro-inflammatory factors, and excessive immune response have been considered as major factors in periodontal disruption. Multiple genes identified in periodontal tissues partly reflect the complexity of the pathogenesis of periodontitis. The effects of novel treatment methods on periodontitis have also been evaluated in a ligature-induced periodontitis model in mice. This model cannot completely represent all aspects of periodontitis in humans but is considered an effective method for the exploration of its mechanisms. Through this review, we aimed to provide evidence and enlightenment for future studies planning to use this model.

Highlights

Periodontitis is an inflammatory disease caused by bacterial biofilms in the periodontal tissues [1]
gastrin-releasing peptide (GRP)-positive cells were mostly located at the oral epithelium of samples from experimental periodontitis model A significant increase in the degree of gingival overgrowth and expansion of the connective tissue area was observed in cyclosporine A (CsA) and ligature-induced periodontal model mice, whereas cessation of CsA and antibiotic administration reduced gingival overgrowth
The results showed that young mice with periodontitis induced by ligation and P. gingivalis LPS had significantly elevated secretion of senescence-associated secretory phenotype (SASP) markers, including pro-inflammatory cytokines tumor necrosis factor α (TNF-α), IL-6, and IL-1β, as well as osteoclastogenic RANKL, and a higher number of osteoclasts compared to periodontitis mice induced by ligature alone

Summary

Introduction

Periodontitis is an inflammatory disease caused by bacterial biofilms in the periodontal tissues [1]. Severe periodontitis leads to tooth loss and has negative effects on other systemic diseases [3]. In the past few decades, a variety of periodontitis models in mice have been established and effectively applied to the exploration of the mechanism of periodontitis and the effectiveness of new treatments [4,5]. Unlike other periodontitis models in mice, the ligature-induced periodontitis model shows acute alveolar bone loss and soft tissue inflammation in the initial period (within seven days), and the healing process of periodontitis can be studied by ligature removal [6,7]. Additional bacterial administration in mice with ligature-induced periodontitis showed an increase in the severity of periodontitis [9,10]

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