Stimulation of bone formation in the expanding premaxillary suture with a GSK-3β inhibitor.

OBJECTIVES

Glycogen synthase kinase-3β (GSK-3β)/β-catenin signaling mediates osteogenesis in response to mechanical loading. We tested the hypothesis that local administration of a GSK-3β inhibitor could stimulate new bone formation in the expanding premaxillary suture.

MATERIALS AND METHODS

Thirty-five Sprague-Dawley rats were subjected to premaxillary suture expansion using a helix spring. The experimental rats were given one or two local injections of SB-415286, a small-molecule GSK-3β inhibitor. Animals were administered calcein and sacrificed on day 7 to quantify new bone formation. To evaluate the proliferation and differentiation of osteoblasts, rats were labeled with bromodeoxyuridine on day 1 and sacrificed on day 2 or 4. β-catenin expression was evaluated by immunohistochemical staining.

RESULTS

Two injections of SB-415286 led to an elevation of β-catenin expression and an increase in the number of proliferating osteoblasts in expanding sutures on day 2 and day 4. Consequently, new bone formation in the suture increased significantly on day 7.

CONCLUSIONS

These results suggest that local delivery of a GSK-3β inhibitor could stimulate bone formation in the expanding premaxillary suture by eliciting β-catenin signaling. GSK-3β could be a pharmaceutical target for improving the effect of orthodontic treatments such as rapid palatal expansion.