Periodontitis induces bone formation around alveolar bone in mice.

Abstract

OBJECTIVES: Periodontitis is a chronic inflammatory disease, characterized by alveolar bone resorption and mediated by osteoclast activation. Clinical reports and cone-beam computed tomography (CT) analyses have noted the presence of thickened bone structures, known as buttressing bone formation, around inflammatory lesions. However, clinical frequency, extent, and mechanisms of new bone formation have not been fully elucidated. To elucidate the inflammation-induced mechanisms of buttressing bone formation, a ligature-induced mouse model of periodontitis was examined. METHODS: Marginal periodontitis model mice were established by silk thread ligation around the right maxillary second molar, and an apical periodontitis model was established by removing the dental pulp, using eight-week-old male C57BL/6J mice. Subcutaneous anti-receptor activator of nuclear factor kappa B ligand (RANKL) antibody injections were performed on Days 0 and 7, then μCT, histological, and histomorphometric analyses were performed. RESULTS: The mice in both models had inflammation-induced bone resorption, accompanied by new bone formation along the outer surface of the alveolar bone. Newly-formed bone in the apical and buccal regions, and extensive osteoclastic and osteoblastic activities were observed throughout the alveolar bone. Inhibition of RANKL suppressed bone resorption and formation, whereas newly-formed bone maintained its structure and mass, even after suture had removed. CONCLUSIONS: The regulation of inflammation-induced bone formation by RANKL-dependent osteoclast activity has been shown in a mouse model of periodontitis. This newly-reported mechanism of bone formation may be maintained by a combination of modelling-based bone apposition and remodelling-based coupling via osteoclasts and osteoblasts. The findings highlight the importance of three-dimensional analysis of bone morphology as part of routine periodontal diagnosis.