Effects of a Glycogen Synthase Kinase 3 Inhibitor Tideglusib on Bone Regeneration With Calvarial Defects

Abstract

Tideglusib is a glycogen synthase kinase 3 (GSK-3) inhibitor which has shown the effects of bone regeneration, used for the treatment of Alzheimer disease. The aim of the study was to determine the effects of Tideglusib in the apoptosis and the bone regeneration in rats with calvarial defects. Twenty male Wistar rats (aged 11-13 weeks) were used for the study. Full-thickness flap elevated to exposure calvarial bone. Two 5 mm critical size calvarial defects were created on each rat calvarium. The defects were divided into 4 study groups: 1-Control (n = 10); 2- Gelatin sponge+Tideglusib (Gs+TDG; n = 10); 3- Autogenous bone (AB; n = 10); 4-Autogenous bone+Tideglusib (AB+TDG; n = 10). Then, the rats were sacrificed at fourth week. Three-dimensional imaging, histopathologic and immunohistochemical examinations were performed to evaluate the samples. The most increased bone formation and interaction between graft and new bone were observed in AB+TDG group. Bone morphogenic protein-2 (BMP-2), alkaline phosphatase (ALP), collagen type 1 (Col 1) and osteocalcin (OCN) was determined significantly higher in Tideglusib received groups compared with those of Control and AB groups (P < 0.05). Osteoclast numbers found to be higher in Gs+TDG and AB+TDG groups as well as RANKL expression dis not affected in Gs+TDG group but decreased in AB+TDG group comparing those of Control and AB groups. In addition, Tideglusib increased the Bcl-2 levels (P < 0.05) and decreased Bax levels (P > 0.05) in Tideglusib received groups compared with their controls. The administration of Tideglusib in calvarial bone defects increased bone mineral density, new bone area and total bone area by decreasing apoptosis and increasing osteoblastogenesis.