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

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. Adul...

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Main Authors: Saranda Disha-Ibrahimi, Borut Furlani, Gorazd Drevenšek, Samo Hudoklin, Janja Marc, Irena Prodan Žitnik, Jakob Sajovic, Martina Drevenšek
Format: Article
Language:English
Published: Association of Basic Medical Sciences of Federation of Bosnia and Herzegovina 2023-01-01
Series:Biomolecules & Biomedicine
Subjects:
Online Access:https://www.bjbms.org/ojs/index.php/bjbms/article/view/7523
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author Saranda Disha-Ibrahimi
Borut Furlani
Gorazd Drevenšek
Samo Hudoklin
Janja Marc
Irena Prodan Žitnik
Jakob Sajovic
Martina Drevenšek
author_facet Saranda Disha-Ibrahimi
Borut Furlani
Gorazd Drevenšek
Samo Hudoklin
Janja Marc
Irena Prodan Žitnik
Jakob Sajovic
Martina Drevenšek
author_sort Saranda Disha-Ibrahimi
collection DOAJ
description 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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spelling doaj.art-65c653054842457a9a5b096305504d1d2024-03-15T13:30:46ZengAssociation of Basic Medical Sciences of Federation of Bosnia and HerzegovinaBiomolecules & Biomedicine2831-08962831-090X2023-01-0123110.17305/bjbms.2022.7523Olanzapine decreased osteocyte maturation and Wnt/β-catenin signaling during loading of the alveolar bone in ratsSaranda Disha-Ibrahimi0https://orcid.org/0000-0002-5493-0698Borut Furlani1https://orcid.org/0000-0003-0870-3467Gorazd Drevenšek2https://orcid.org/0000-0002-9254-4931Samo Hudoklin3https://orcid.org/0000-0002-2144-292XJanja Marc4Irena Prodan Žitnik5https://orcid.org/0000-0002-6843-8709Jakob Sajovic6https://orcid.org/0000-0003-1633-5983Martina Drevenšek7https://orcid.org/0000-0003-3366-5706Department of Orthodontics, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia; Department of Periodontology and Oral Medicine, Faculty of Medicine, University of Prishtina, Prishtina, KosovoInstitute of Pharmacology and Experimental Toxicology, Faculty of Medicine, University of Ljubljana, Ljubljana, SloveniaInstitute of Pharmacology and Experimental Toxicology, Faculty of Medicine, University of Ljubljana, Ljubljana, SloveniaInstitute of Cell Biology, Faculty of Medicine, University of Ljubljana, Ljubljana, SloveniaDepartment of Clinical Biochemistry, Faculty of Pharmacy, University of Ljubljana, Ljubljana, SloveniaDepartment of Clinical Biochemistry, Faculty of Pharmacy, University of Ljubljana, Ljubljana, SloveniaInstitute of Pharmacology and Experimental Toxicology, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia; Department of Orthodontics, University Medical Centre Ljubljana, Ljubljana, SloveniaDepartment of Orthodontics, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia; Department of Orthodontics, University Medical Centre Ljubljana, Ljubljana, Slovenia 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. https://www.bjbms.org/ojs/index.php/bjbms/article/view/7523Olanzapineosteocyte maturationbone turnoverbone modelingWnt/β-catenin signaling pathwaorthodontic force
spellingShingle Saranda Disha-Ibrahimi
Borut Furlani
Gorazd Drevenšek
Samo Hudoklin
Janja Marc
Irena Prodan Žitnik
Jakob Sajovic
Martina Drevenšek
Olanzapine decreased osteocyte maturation and Wnt/β-catenin signaling during loading of the alveolar bone in rats
Biomolecules & Biomedicine
Olanzapine
osteocyte maturation
bone turnover
bone modeling
Wnt/β-catenin signaling pathwa
orthodontic force
title Olanzapine decreased osteocyte maturation and Wnt/β-catenin signaling during loading of the alveolar bone in rats
title_full Olanzapine decreased osteocyte maturation and Wnt/β-catenin signaling during loading of the alveolar bone in rats
title_fullStr Olanzapine decreased osteocyte maturation and Wnt/β-catenin signaling during loading of the alveolar bone in rats
title_full_unstemmed Olanzapine decreased osteocyte maturation and Wnt/β-catenin signaling during loading of the alveolar bone in rats
title_short Olanzapine decreased osteocyte maturation and Wnt/β-catenin signaling during loading of the alveolar bone in rats
title_sort olanzapine decreased osteocyte maturation and wnt β catenin signaling during loading of the alveolar bone in rats
topic Olanzapine
osteocyte maturation
bone turnover
bone modeling
Wnt/β-catenin signaling pathwa
orthodontic force
url https://www.bjbms.org/ojs/index.php/bjbms/article/view/7523
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