Wnt5a mediated canonical Wnt signaling pathway activation in orthodontic tooth movement: possible role in the tension force-induced bone formation

Orthodontic tooth movement (OTM) is associated with bone remodeling mediated by orthodontic mechanical loading. Increasing studies reported that Wnt signaling played crucial roles in mechanical stimuli induced bone remodeling. However, little is known about the involvement of Wnt signaling in orthodontic force-induced bone formation during OTM. In virtue of the OTM mice model as we previously reported, where new bone formation was determined by micro-CT and immunoreactivity of osteocalcin and osterix, we explored the activation of Wnt signaling pathway during OTM. Our results proved the nuclei translocation of beta-catenin, suggesting the activation of canonical Wnt signaling pathway in the periodontal ligament cells (PDLCs) near the alveolar bone at the tension site (TS). Moreover, the immunoreactivity of Wnt5a, but not Wnt3a in PDLCs indicated the activation of canonical Wnt pathway might be mediated by Wnt5a, but not Wnt3a as in most cases. The co-location of Wnt5a and beta-catenin that was evidenced by double labeling immunofluorescence staining further supported the hypothesis. In addition, the high expression of FZD4 and LRP5 in PDLCs at TS of periodontium suggested that the activation of Wnt signaling pathway was mediated by these receptors. The negligible expression of ROR2 also indicated that canonical but not non-canonical Wnt signaling pathway was activated by Wnt5a, since previous studies demonstrated that the activation of canonical/non-canonical Wnt signaling pathway was largely dependent on the receptors. In summary, we here reported that Wnt5a mediated activation of canonical Wnt signaling pathway might contribute to the orthodontic force induced bone remodeling.