Vibration accelerates orthodontic tooth movement by inducing osteoclastogenesis via transforming growth factor-ß signalling in osteocytes.

BACKGROUND: We previously found the conditions of supplementary vibration that accelerated tooth movement and induced bone resorption in an experimental rat tooth movement model. However, the molecular biological mechanisms underlying supplementary vibration-induced orthodontic tooth movement are not fully understood. Transforming growth factor (TGF)-ß upregulates osteoclastogenesis via induction of the receptor activator of nuclear factor kappa B ligand expression, thus TGF-ß is considered an essential cytokine to induce bone resorption. OBJECTIVES: The aim of this study is to examine the role of TGF-ß during the acceleration of orthodontic tooth movement by supplementary vibration. MATERIALS AND METHODS: In experimental tooth movement, 15 g of orthodontic force was loaded onto the maxillary right first molar for 28 days. Supplementary vibration (3 g, 70 Hz) was applied to the maxillary first molar for 3 min on days 0, 7, 14, and 21. TGF-ß receptor inhibitor SB431542 was injected into the submucosal palatal and buccal areas of the maxillary first molars once every other day. The co-culture of RAW264.7 cells and MLO-Y4 cells was used as an in vitro osteoclastogenesis model. RESULTS: SB431542 suppressed the acceleration of tooth movement and the increase in the number of osteoclasts by supplementary vibration in our experimental rat tooth movement model. Immunohistochemical analysis showed supplementary vibration increased the number of TGF-ß1-positive osteocytes in the alveolar bone on the compression side during the experimental tooth movement. Moreover, vibration-upregulated TGF-ß1 in MLO-Y4 cells induced osteoclastogenesis. CONCLUSIONS: Orthodontic tooth movement was accelerated by supplementary vibration through the promotion of the production of TGF-ß1 in osteocytes and subsequent osteoclastogenesis.

Three-Dimensional Evaluation of Treatment Effects and Post-Treatment Stability of Maxillary Molar Intrusion Using Temporary Anchorage Devices in Open Bite Malocclusion.

Background: We investigated treatment outcomes and post-treatment stability in 10 patients with an anterior open bite and nonsurgical orthodontics. Methods: The patients underwent maxillary molar intrusion using temporary anchorage devices (TADs) to deepen the overbite due to mandibular autorotation. Lateral cephalograms and dental cast models were obtained before treatment (T0), immediately after it (T1), and >1 year after it (T2). Skeletal and dental cephalometric changes and three-dimensional movements of the maxillary dentitions were evaluated. Results: At T0, cephalometric analysis indicated that patients had skeletal class I with tendencies for a class II jaw relationship and a skeletal open bite. During active treatment (T0 to T1), the maxillary first molar intruded by 1.6 mm, the mandibular first molar extruded by 0.3 mm, the Frankfort-mandibular plane angle decreased by 1.1°, and the overbite increased by 4.1 mm. Statistically significant changes were observed in the amount of vertical movement of the maxillary first molar, Frankfort-mandibular plane angle, and overbite. Three-dimensional (3D) dental cast analysis revealed that the maxillary first and second molars intruded, whereas the anterior teeth extruded, with the second premolar as an infection point. In addition, the maxillary molar was tipped distally by 2.9° and rotated distally by 0.91°. Statistically significant changes were observed in the amount of vertical movement of the central incisor, lateral incisor, canine and first molar, and molar angulation. From T1 to T2, no significant changes in cephalometric measurements or the 3D position of the maxillary dentition were observed. The maxillary and mandibular dentitions did not significantly change during post-treatment follow-up. Conclusions: Maxillary molar intrusion using mini-screws is an effective treatment for open bite correction, with the achieved occlusion demonstrating 3D stability at least 1 year after treatment.

Three-dimensional morphologic analysis of the maxillary alveolar bone after anterior tooth retraction with temporary anchorage devices.

OBJECTIVES: To investigate three-dimensional (3D) morphologic changes in the alveolar bone around the maxillary central incisors of patients who underwent premolar extraction and subsequent anterior tooth retraction using temporary anchorage devices (TADs). MATERIALS AND METHODS: The subjects consisted of 16 patients with bimaxillary protrusion. The maxillary anterior teeth were retracted using sliding or loop mechanics and TADs for anchorage reinforcement. Cephalograms and computed tomography scans taken pretreatment and posttreatment were registered with respect to the palatal structures. The movement of the maxillary central incisors and morphologic changes in the anterior alveolar bone were evaluated quantitatively. RESULTS: Displacement in the palatal direction was observed in the alveolar bone around the incisors and the interdental septum. The displacement and bone remodeling/tooth movement ratio were larger on the labial side than the palatal side, and decreased progressively from the crest to apex level. The bone thickness was significantly increased on the labial side and decreased on the palatal side. CONCLUSIONS: Regional differences exist in morphologic changes of the alveolar bone during anterior tooth retraction using TADs. Attention should be paid to the crest region of the palatal alveolar bone because of its small original thickness and low remodeling activity.

Insulin-like growth factor 1 modulates bioengineered tooth morphogenesis.

Regenerative therapy to replace missing teeth is a critical area of research. Functional bioengineered teeth have been produced by the organ germ method using mouse tooth germ cells. However, these bioengineered teeth are significantly smaller in size and exhibit an abnormal crown shape when compared with natural teeth. The proper sizes and shapes of teeth contribute to their normal function. Therefore, a method is needed to control the morphology of bioengineered teeth. Here, we investigated whether insulin-like growth factor 1 (IGF1) can regulate the sizes and shapes of bioengineered teeth, and assessed underlying mechanisms of such regulation. IGF1 treatment significantly increased the size of bioengineered tooth germs, while preserving normal tooth histology. IGF1-treated bioengineered teeth, which were developed from bioengineered tooth germs in subrenal capsules and jawbones, showed increased sizes and cusp numbers. IGF1 increased the number of fibroblast growth factor (Fgf4)-expressing enamel knots in bioengineered tooth germs and enhanced the proliferation and differentiation of dental epithelial and mesenchymal cells. This study is the first to reveal that IGF1 increases the sizes and cusp numbers of bioengineered teeth via the induction of enamel knot formation, as well as the proliferation and differentiation of dental epithelial and mesenchymal cells.

Differentiation of Odontoblast-Like Cells From Mouse Induced Pluripotent Stem Cells by Pax9 and Bmp4 Transfection.

UNLABELLED: The field of tooth regeneration has progressed in recent years, and human tooth regeneration could become viable in the future. Because induced pluripotent stem (iPS) cells can differentiate into odontogenic cells given appropriate conditions, iPS cells are a potential cell source for tooth regeneration. However, a definitive method to induce iPS cell-derived odontogenic cells has not been established. We describe a novel method of odontoblast differentiation from iPS cells using gene transfection. We generated mouse iPS cell-derived neural crest-like cells (iNCLCs), which exhibited neural crest markers. Next, we differentiated iNCLCs into odontoblast-like cells by transfection of Pax9 and Bmp4 expression plasmids. Exogenous Pax9 upregulated expression of Msx1 and dentin matrix protein 1 (Dmp1) in iNCLCs but not bone morphogenetic protein 4 (Bmp4) or dentin sialophosphoprotein (Dspp). Exogenous Bmp4 upregulated expression of Msx1, Dmp1, and Dspp in iNCLCs, but not Pax9. Moreover, cotransfection of Pax9 and Bmp4 plasmids in iNCLCs revealed a higher expression of Pax9 than when Pax9 plasmid was used alone. In contrast, exogenous Pax9 downregulated Bmp4 overexpression. Cotransfection of Pax9 and Bmp4 synergistically upregulated Dmp1 expression; however, Pax9 overexpression downregulated exogenous Bmp4-induced Dspp expression. Together, these findings suggest that an interaction between exogenous Pax9- and Bmp4-induced signaling modulated Dmp1 and Dspp expression. In conclusion, transfection of Pax9 and Bmp4 expression plasmids in iNCLCs induced gene expression associated with odontoblast differentiation, suggesting that iNCLCs differentiated into odontoblast-like cells. The iPS cell-derived odontoblast-like cells could be a useful cell source for tooth regeneration. SIGNIFICANCE: It has been reported that induced pluripotent stem (iPS) cells differentiate into odontogenic cells by administration of recombinant growth factors and coculture with odontogenic cells. Therefore, they can be potential cell sources for tooth regeneration. However, these previous methods still have problems, such as usage of other cell types, heterogeneity of differentiated cells, and tumorigenicity. In the present study, a novel method to differentiate iPS cells into odontoblast-like cells without tumorigenicity using gene transfection was established. It is an important advance in the establishment of efficient methods to generate homogeneous functional odontogenic cells derived from iPS cells.