Department of Orthodontics, Ninth People's Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, China.
Oral Dis. 2013 Jan;19(1):73-9. doi: 10.1111/j.1601-0825.2012.01957.x. Epub 2012 Jul 8.
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.
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.
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.
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.
糖原合成酶激酶-3β（GSK-3β）/β-连环蛋白信号通路介导了机械加载刺激成骨作用。我们假设局部给予 GSK-3β 抑制剂可刺激扩张前上颌骨缝中的新骨形成。
35 只 Sprague-Dawley 大鼠采用螺旋簧行前上颌骨缝扩张。实验组大鼠给予一次或两次局部注射小分子 GSK-3β 抑制剂 SB-415286。动物给予钙黄绿素，于第 7 天处死以定量新骨形成。为了评估成骨细胞的增殖和分化，大鼠于第 1 天接受溴脱氧尿苷标记，于第 2 天或第 4 天处死。通过免疫组织化学染色评估β-连环蛋白表达。
两次注射 SB-415286 导致第 2 天和第 4 天扩张缝中β-连环蛋白表达升高和增殖性成骨细胞数量增加。因此，第 7 天缝中的新骨形成显著增加。
这些结果表明，局部给予 GSK-3β 抑制剂可通过激活β-连环蛋白信号通路刺激扩张前上颌骨缝中的骨形成。GSK-3β 可能成为改善正畸治疗效果的药物靶点，如快速腭扩张。
