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

Abstract

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 β-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 β-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.

TAZ contributes to osteogenic differentiation of periodontal ligament cells under tensile stress

“…Although it has been well established that the canonical Wnt/β‐catenin signaling is of great importance for mechanosensation and mechanotransduction in osteogenic commitment of osteocytes, there still exists limited evidence with regard to the involvement of Wnt signaling in the orthodontic force‐induced osteogenic differentiation of PDLCs. It was found that when subjected to stretch force during OTM in murine model, the nucleus translocation of β‐catenin was distinctly increased in the PDLCs at the tension side of periodontium, which contributes to novel bone formation . On the other hand, in vitro study reported that β‐catenin may also serve as the effector of compressive loading in PDLCs .…”

“…It was found that when subjected to stretch force during OTM in murine model, the nucleus translocation of β-catenin was distinctly increased in the PDLCs at the tension side of periodontium, which contributes to novel bone formation. 31 On the other hand, in vitro study reported that β-catenin may also serve as the effector of compressive loading in PDLCs. 16 Consistently, we confirmed the activation of the 33 In the present study, depletion of TAZ using siRNA offset the CTS-induced osteogenic differentiation and Wnt-related protein expressions, indirectly suggesting that TAZ could be the upstream element of Wnt/β-catenin signaling in the process of CTS osteogenesis.…”

Osteocytes and mechanical loading: The Wnt connection

“…In mice subjected to tooth movement via and open-coil spring, Lrp5 and Fzd4 (a Wnt co-receptor) were upregulated in the periodontium near alveolar bone. 20 In addition, the downstream canonical mediator β-catenin was also activated in the same tissues by tooth movement. Moreover, Lrp5-HBM mice exhibit an increase in alveolar bone formation, and narrowing of the PDL space.…”

“…However, accumulating data suggests that Wnt signalling is also important in alveolar bone for tooth movement. In mice subjected to tooth movement via and open‐coil spring, Lrp5 and Fzd4 (a Wnt co‐receptor) were upregulated in the periodontium near alveolar bone . In addition, the downstream canonical mediator β‐catenin was also activated in the same tissues by tooth movement.…”

Exploiting the WNT Signaling Pathway for Clinical Purposes

“…The findings include regulation of pulp volume and dentin thickness [110], enhancement of dentin regeneration [111], and cementum regeneration [112]. Tooth movement during orthodontic treatment has also been shown to involve activation of Wnt signaling [113,114]. All of these have been shown to involve the Wnt signaling pathway.…”