title: Stimulation of bone formation in the expanding premaxillary suture with a GSK-3β inhibitor.
abstract: OBJECTIVE
  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.
  
  
  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.
authors: Department of Orthodontics, Ninth People's Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, China.
authors: Y
authors: Y
authors: Jiang
authors: H X
authors: HX
authors: Liu
authors: J J
authors: JJ
authors: Guo
authors: G H
authors: GH
authors: Tang
authors: Y F
authors: YF
authors: Qian
mesh_terms: D000627:Aminophenols / Q000494:pharmacology; D000818:Animals; D000963:Antimetabolites; D001973:Bromodeoxyuridine; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D003393:Cranial Sutures / Q000187:drug effects*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005452:Fluoresceins; D005456:Fluorescent Dyes; D038362:Glycogen Synthase Kinase 3 / Q000037:antagonists & inhibitors*; D000071679:Glycogen Synthase Kinase 3 beta; D008297:Male; D008301:Maleimides / Q000494:pharmacology; D008437:Maxilla / Q000187:drug effects*; D010006:Osteoblasts / Q000187:drug effects; D010012:Osteogenesis / Q000187:drug effects*; D010155:Palatal Expansion Technique / Q000295:instrumentation; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D051176:beta Catenin / Q000032:analysis / Q000187:drug effects
chemical_list: C417520:3-(3-chloro-4-hydroxyphenylamino)-4-(4-nitrophenyl)-1H-pyrrole-2,5-dione; D000627:Aminophenols; D000963:Antimetabolites; C495268:Ctnnb1 protein, rat; D004791:Enzyme Inhibitors; D005452:Fluoresceins; D005456:Fluorescent Dyes; D008301:Maleimides; D051176:beta Catenin; C083098:calcein green; D000071679:Glycogen Synthase Kinase 3 beta; C000605508:Gsk3b protein, rat; D038362:Glycogen Synthase Kinase 3; D001973:Bromodeoxyuridine