Department of Orthodontics, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia; Department of Periodontology and Oral Medicine, Faculty of Medicine, University of Prishtina, Prishtina, Kosovo.
Institute of Pharmacology and Experimental Toxicology, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia.
Biomol Biomed. 2023 Feb 1;23(1):114-125. doi: 10.17305/bjbms.2022.7523.
Several studies indicate the influence of olanzapine on bone metabolism; however, the results are contradictory. We evaluated the effects of olanzapine on the Wnt/β-catenin signaling pathway, physiological alveolar bone turnover, and alveolar bone modeling due to an applied orthodontic force. Adult male rats (n=48) were treated with either olanzapine or a vehicle for 21 days; then 8 rats from each group were sacrificed and the rest were divided into 4 groups: control, appliance-only, olanzapine-only, and olanzapine-appliance. The rats in the appliance groups were mounted with a superelastic closed coil spring that maintained constant orthodontic force between molars and incisors. We studied the effects of olanzapine on physiological alveolar bone turnover on day 21 of the experiment, and on alveolar bone modeling due to orthodontic force on day 56. We determined tooth movement, alveolar bone volume, activity of bone-specific cells, serum alkaline phosphatase (ALP) activity, and gene expression levels of Wnt/β-catenin signaling target genes. During forced bone modeling, olanzapine increased osteoblast volume (P<0.0001) and ALP activity (P=0.0011) and decreased osteoclast volume (P<0.0001) and gene expression of the Wnt/β-catenin signaling target genes Fosl1, Axin2, and Dkk1(P=0.001, P=0.0076, and P=0.036, respectively), and the osteocyte markers Sost and Dmp1 (P=0.0432 and P=0.0021, respectively). Similar results were obtained during physiological alveolar bone turnover on day 21, when olanzapine downregulated the gene expression of osteocyte markers and Wnt/β-catenin signaling target genes. We concluded that olanzapine attenuated osteocyte maturation during forced bone modeling and physiological alveolar bone turnover, potentially through downregulation of the Wnt/β-catenin signaling pathway.
几项研究表明奥氮平对骨代谢有影响；然而，结果却是相互矛盾的。我们评估了奥氮平对 Wnt/β-连环蛋白信号通路、生理牙槽骨转换以及由于应用正畸力导致的牙槽骨建模的影响。成年雄性大鼠（n=48）用奥氮平或载体处理 21 天；然后每组 8 只大鼠被处死，其余大鼠分为 4 组：对照组、仅用器械组、仅用奥氮平组和奥氮平加器械组。器械组的大鼠安装超弹性封闭线圈弹簧，在磨牙和切牙之间保持恒定的正畸力。我们研究了奥氮平在实验第 21 天对生理牙槽骨转换的影响，以及在第 56 天对正畸力导致的牙槽骨建模的影响。我们确定了牙齿移动、牙槽骨体积、骨特异性细胞活性、血清碱性磷酸酶（ALP）活性以及 Wnt/β-连环蛋白信号靶基因的表达水平。在强制骨建模过程中，奥氮平增加了成骨细胞体积（P<0.0001）和 ALP 活性（P=0.0011），减少了破骨细胞体积（P<0.0001）和 Wnt/β-连环蛋白信号靶基因 Fosl1、Axin2 和 Dkk1 的基因表达（P=0.001、P=0.0076 和 P=0.036），以及骨细胞标记物 Sost 和 Dmp1（P=0.0432 和 P=0.0021）。在第 21 天的生理牙槽骨转换期间也得到了类似的结果，当时奥氮平下调了骨细胞标记物和 Wnt/β-连环蛋白信号靶基因的基因表达。我们得出结论，奥氮平在强制骨建模和生理牙槽骨转换过程中减弱了骨细胞的成熟，这可能是通过下调 Wnt/β-连环蛋白信号通路实现的。
