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.

The role of TRPV2 as a regulator on the osteoclast differentiation during orthodontic tooth movement in rats.

When orthodontic forces are applied to teeth, bone remodeling, which consists of bone resorption and bone formation, occurs around the teeth. Transient receptor potential vanilloid 2 (TRPV2) is a cation channel expressed in various cell types that responds to various stimuli, including mechanical stress, and involved in calcium oscillations during the early stages of osteoclast differentiation. However, in vivo expression of TRPV2 in osteoclasts has not yet been reported, and temporo-spatial expression of TRPV2 during osteoclast differentiation is unclear. In this study, we examined the TRPV2 expression during experimental tooth movement and assessed the effect of TRPV2 on osteoclast differentiation. TRPV2 was detected on day 1 after experimental tooth movement on the compression side, and the number of TRPV2-expressing cells significantly increased on day 7. These TRPV2-expressing cells had a single, or multiple nuclei and were positive for TRAP activity. Consistent with these in vivo findings, in vitro experiments using RAW264.7 osteoclast progenitor cells showed that TRPV2 mRNA was increased at the early stage of osteoclast differentiation and maintained until the late stage. Furthermore, a TRPV2 channel selective antagonist significantly inhibited osteoclast differentiation. These findings suggest that TRPV2 may have a regulatory role in osteoclast differentiation during orthodontic tooth movement.

Vibration enhances osteoclastogenesis by inducing RANKL expression via NF-κB signaling in osteocytes.

To shorten the duration of orthodontic treatment it is important not only to reduce risks such as dental caries, periodontal disease, and root resorption, but also to decrease pain and discomfort caused by a fixed appliance. Several studies have investigated the effect of vibration applied to fixed appliances to accelerate tooth movement. Although it was reported that vibration accelerates orthodontic tooth movement by enhancing alveolar bone resorption, the underlying cellular and molecular mechanisms remain unclear. In this study, we investigated the effects of vibration on osteoclastogenesis in vitro and in vivo. Vibration applied to pre-osteoclast cell line RAW264.7 cells enhanced cell proliferation but did not affect their differentiation into osteoclasts. Osteocytes in bone are known to be mechanosensitive and to act as receptor activator of nuclear factor kappa B (NF-κB) ligand (RANKL). Therefore, in the present study, vibration was applied to cells from the osteocyte-like cell line MLO-Y4. In MLO-Y4 cells, vibration induced phosphorylation of the inhibitor of NF-κB (IκB) and caused nuclear localization of NF-κB p65. Additionally, vibration increased RANKL mRNA expression, but did not affect osteoprotegerin (OPG) mRNA expression in MLO-Y4 cells, thus resulting in an increased RANKL/OPG ratio. Consistent with these findings, vibration applied during experimental tooth movement increased NF-κB activation and RANKL expression in osteocytes on the compression side of alveolar bone in vivo, whereas vibration had no such effects on the tension side. Furthermore, in a co-culture of MLO-Y4 cells and RAW264.7 cells, vibration applied to MLO-Y4 cells enhanced osteoclastogenesis. These findings suggest that vibration could accelerate orthodontic tooth movement by enhancing osteoclastogenesis through increasing the number of pre-osteoclasts and up-regulating RANKL expression in osteocytes on the compression side of alveolar bone via NF-κB activation.