Lektemur Alpan Aysan, Çalişir Metin, Kizildağ Alper, Özdede Melih, Özmen Özlem
Department of Periodontology, Faculty of Dentistry, Pamukkale University, Denizli.
Department of Periodontology, Faculty of Dentistry, Adiyaman University, Adiyaman.
J Craniofac Surg. 2020 Jul-Aug;31(5):1477-1482. doi: 10.1097/SCS.0000000000006326.
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.
Tideglusib是一种糖原合酶激酶3（GSK-3）抑制剂，已显示出骨再生作用，用于治疗阿尔茨海默病。本研究的目的是确定Tideglusib对大鼠颅骨缺损模型中细胞凋亡和骨再生的影响。选用20只11-13周龄的雄性Wistar大鼠进行研究。掀起全层皮瓣以暴露颅骨。在每只大鼠的颅骨上制造两个5毫米的临界尺寸颅骨缺损。将缺损分为4个研究组：1-对照组（n = 10）；2-明胶海绵+Tideglusib（Gs+TDG；n = 10）；3-自体骨（AB；n = 10）；4-自体骨+Tideglusib（AB+TDG；n = 10）。然后，在第四周处死大鼠。进行三维成像、组织病理学和免疫组织化学检查以评估样本。在AB+TDG组中观察到骨形成增加最多，且移植物与新骨之间的相互作用最强。与对照组和AB组相比，接受Tideglusib治疗的组中骨形态发生蛋白-2（BMP-2）、碱性磷酸酶（ALP）、I型胶原（Col 1）和骨钙素（OCN）的含量显著更高（P < 0.05）。发现Gs+TDG组和AB+TDG组中的破骨细胞数量较高，与对照组和AB组相比，Gs+TDG组中的RANKL表达未受影响，但AB+TDG组中的RANKL表达降低。此外，与对照组相比，接受Tideglusib治疗的组中Tideglusib增加了Bcl-2水平（P < 0.05）并降低了Bax水平（P > 0.05）。在颅骨缺损处给予Tideglusib可通过减少细胞凋亡和增加成骨细胞生成来提高骨矿物质密度、新骨面积和总骨面积。
