Excessive Orthodontic Force Induces Odontoclastogenesis in Root Cementum as Evidenced by the Expression of RANK/RANKL

Abstract

The differentiation and functions of osteoclasts are regulated by the receptor activator of nuclear factor kappa beta (RANK) and its ligand (RANKL). The present study was designed to identify the expression of RANK/RANKL in the event of root resorption provoked by excessive orthodontic force and also to explore the biological mechanism of the RANK/RANKL system in regulating odontoclastogenesis in root cementum. Thirty male Wistar rats were subjected to orthodontic force of 100 g to induce a mesially tipping movement of the left mandibular first molars. The contralateral molars served as intraindividual controls. The rats were sacrificed after 3, 7, or 10 days. The mandibular body surrounding the molars was harvested and serial sections of 6-μm thickness were cut. Immunohistochemical assays were conducted to localize the expression of RANK/RANKL proteins and histomorphological examination was undertaken to identify cellular response in cementum, periodontal ligament, and alveolar bone during root resorption. Root resorption in cementum occurred at the sites corresponding to compression of the periodontal ligament, indicated by increased numbers of multinucleated osteoclasts and odontoclasts. Immunoreaction against RANKL became stronger in osteoblasts, osteoclasts, odontoclasts, and fibroblasts of the periodontal ligament from Day 3 onwards. The number of positively immunoreactive cells against RANK also increased significantly over Days 3, 7, and 10 (p<0.01). The RANK/RANKL system is responsible for transducing the heavy mechanical loading signals into an odontoclastic episode in root resorption.