Olanzapine decreased osteocyte maturation and Wnt/β-catenin signaling during loading of the alveolar bone in rats

Authors

  • Saranda Disha-Ibrahimi Department of Orthodontics, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia; Department of Periodontology and Oral Medicine, Faculty of Medicine, University of Prishtina, Kosovo https://orcid.org/0000-0002-5493-0698
  • Borut Furlani Institute of Pharmacology and Experimental Toxicology, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia https://orcid.org/0000-0003-0870-3467
  • Gorazd Drevenšek Institute of Pharmacology and Experimental Toxicology, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia https://orcid.org/0000-0002-9254-4931
  • Samo Hudoklin Institute of Cell Biology, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia https://orcid.org/0000-0002-2144-292X
  • Janja Marc Department of Clinical Biochemistry, Faculty of Pharmacy, University of Ljubljana, Ljubljana, Slovenia
  • Irena Prodan Žitnik Department of Clinical Biochemistry, Faculty of Pharmacy, University of Ljubljana, Ljubljana, Slovenia https://orcid.org/0000-0002-6843-8709
  • Jakob Sajovic Institute of Pharmacology and Experimental Toxicology, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia; Department of Orthodontics, University Medical Centre Ljubljana, Ljubljana, Slovenia https://orcid.org/0000-0003-1633-5983
  • Martina Drevenšek Department of Orthodontics, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia; Department of Orthodontics, University Medical Centre Ljubljana, Ljubljana, Slovenia https://orcid.org/0000-0003-3366-5706

DOI:

https://doi.org/10.17305/bjbms.2022.7523

Keywords:

Olanzapine, osteocyte maturation, bone turnover, bone modeling, Wnt/β-catenin signaling pathwa, orthodontic force

Abstract

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.

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Olanzapine decreased osteocyte maturation and Wnt/β-catenin signaling during loading of the alveolar bone in rats

Published

2022-07-19

How to Cite

1.
Disha-Ibrahimi S, Furlani B, Drevenšek G, Hudoklin S, Marc J, Prodan Žitnik I, Sajovic J, Drevenšek M. Olanzapine decreased osteocyte maturation and Wnt/β-catenin signaling during loading of the alveolar bone in rats. Bosn J of Basic Med Sci [Internet]. 2022Jul.19 [cited 2022Aug.18];. Available from: https://www.bjbms.org/ojs/index.php/bjbms/article/view/7523

Issue

Section

Molecular Biology