Enamel biomineralization under the effects of indomethacin and celecoxib non-steroidal anti-inflammatory drugs

Abstract The aim of this study was to explore the effects of nonsteroidal anti-inflammatory drugs on biomineralization of enamel. Sixty C57Bl6 male mice were used, which were assigned into three groups: celecoxib (n = 20) or indomethacin (n = 20) treatment for a period of 28 days or received no medi...

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Main Authors: Juliana de Lima Gonçalves, Ana Caroline Alves Duarte, Luciano Aparecido Almeida-Junior, Fabrício Kitazono de Carvalho, Alexandra Mussolino de Queiroz, Maya Fernanda Manfrin Arnez, Lúcia Helena Faccioli, Francisco Wanderley Garcia Paula-Silva
Format: Article
Language:English
Published: Nature Portfolio 2022-09-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-022-19583-w
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author Juliana de Lima Gonçalves
Ana Caroline Alves Duarte
Luciano Aparecido Almeida-Junior
Fabrício Kitazono de Carvalho
Alexandra Mussolino de Queiroz
Maya Fernanda Manfrin Arnez
Lúcia Helena Faccioli
Francisco Wanderley Garcia Paula-Silva
author_facet Juliana de Lima Gonçalves
Ana Caroline Alves Duarte
Luciano Aparecido Almeida-Junior
Fabrício Kitazono de Carvalho
Alexandra Mussolino de Queiroz
Maya Fernanda Manfrin Arnez
Lúcia Helena Faccioli
Francisco Wanderley Garcia Paula-Silva
author_sort Juliana de Lima Gonçalves
collection DOAJ
description Abstract The aim of this study was to explore the effects of nonsteroidal anti-inflammatory drugs on biomineralization of enamel. Sixty C57Bl6 male mice were used, which were assigned into three groups: celecoxib (n = 20) or indomethacin (n = 20) treatment for a period of 28 days or received no medication (control group, n = 20). Visual inspection and microcomputed tomography were used to analyze enamel morphology. Scanning electron microscopy–Energy dispersive X-ray and Knoop microhardness test were used to quantify chemical element content (Ca, P, C, O) and enamel microhardness, respectively. Tissues were collected to investigate the synthesis, activity or nuclear translocation of metalloproteinase-20, transcription factor Runx2, dentin sialoprotein and cyclooxygenase-2 enzyme by means of immunohistochemistry, in situ zymography and indirect immunofluorescence. Treatment with indomethacin and celecoxib reduced the Ca and P content, microhardness and mineral density in enamel. Treatment with nonsteroidal anti-inflammatory drugs caused an accumulation of metalloproteinase-20 and overall increased enzymatic activity in enamel matrix, while the synthesis of the transcription factor Runx2 was inhibited by these drugs. Interestingly, indomethacin inhibited Runx2 translocation to the nucleus whereas celecoxib did not. Those findings show that non-steroidal anti-inflammatory drugs impact the enamel biomineralization and could be involved in the etiology tooth enamel defects if used during the period of tooth formation and mineralization.
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spelling doaj.art-3d4b551b4706481a8d4a8201aa9be0f22022-12-22T03:48:06ZengNature PortfolioScientific Reports2045-23222022-09-0112111310.1038/s41598-022-19583-wEnamel biomineralization under the effects of indomethacin and celecoxib non-steroidal anti-inflammatory drugsJuliana de Lima Gonçalves0Ana Caroline Alves Duarte1Luciano Aparecido Almeida-Junior2Fabrício Kitazono de Carvalho3Alexandra Mussolino de Queiroz4Maya Fernanda Manfrin Arnez5Lúcia Helena Faccioli6Francisco Wanderley Garcia Paula-Silva7Departament of Pediatric Clinics, School of Dentistry of Ribeirão Preto at University of São PauloDepartament of Pediatric Clinics, School of Dentistry of Ribeirão Preto at University of São PauloDepartament of Pediatric Clinics, School of Dentistry of Ribeirão Preto at University of São PauloDepartament of Pediatric Clinics, School of Dentistry of Ribeirão Preto at University of São PauloDepartament of Pediatric Clinics, School of Dentistry of Ribeirão Preto at University of São PauloDepartament of Pediatric Clinics, School of Dentistry of Ribeirão Preto at University of São PauloDepartamento de Análises Clínicas, Toxicológicas e Bromatológicas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São PauloDepartament of Pediatric Clinics, School of Dentistry of Ribeirão Preto at University of São PauloAbstract The aim of this study was to explore the effects of nonsteroidal anti-inflammatory drugs on biomineralization of enamel. Sixty C57Bl6 male mice were used, which were assigned into three groups: celecoxib (n = 20) or indomethacin (n = 20) treatment for a period of 28 days or received no medication (control group, n = 20). Visual inspection and microcomputed tomography were used to analyze enamel morphology. Scanning electron microscopy–Energy dispersive X-ray and Knoop microhardness test were used to quantify chemical element content (Ca, P, C, O) and enamel microhardness, respectively. Tissues were collected to investigate the synthesis, activity or nuclear translocation of metalloproteinase-20, transcription factor Runx2, dentin sialoprotein and cyclooxygenase-2 enzyme by means of immunohistochemistry, in situ zymography and indirect immunofluorescence. Treatment with indomethacin and celecoxib reduced the Ca and P content, microhardness and mineral density in enamel. Treatment with nonsteroidal anti-inflammatory drugs caused an accumulation of metalloproteinase-20 and overall increased enzymatic activity in enamel matrix, while the synthesis of the transcription factor Runx2 was inhibited by these drugs. Interestingly, indomethacin inhibited Runx2 translocation to the nucleus whereas celecoxib did not. Those findings show that non-steroidal anti-inflammatory drugs impact the enamel biomineralization and could be involved in the etiology tooth enamel defects if used during the period of tooth formation and mineralization.https://doi.org/10.1038/s41598-022-19583-w
spellingShingle Juliana de Lima Gonçalves
Ana Caroline Alves Duarte
Luciano Aparecido Almeida-Junior
Fabrício Kitazono de Carvalho
Alexandra Mussolino de Queiroz
Maya Fernanda Manfrin Arnez
Lúcia Helena Faccioli
Francisco Wanderley Garcia Paula-Silva
Enamel biomineralization under the effects of indomethacin and celecoxib non-steroidal anti-inflammatory drugs
Scientific Reports
title Enamel biomineralization under the effects of indomethacin and celecoxib non-steroidal anti-inflammatory drugs
title_full Enamel biomineralization under the effects of indomethacin and celecoxib non-steroidal anti-inflammatory drugs
title_fullStr Enamel biomineralization under the effects of indomethacin and celecoxib non-steroidal anti-inflammatory drugs
title_full_unstemmed Enamel biomineralization under the effects of indomethacin and celecoxib non-steroidal anti-inflammatory drugs
title_short Enamel biomineralization under the effects of indomethacin and celecoxib non-steroidal anti-inflammatory drugs
title_sort enamel biomineralization under the effects of indomethacin and celecoxib non steroidal anti inflammatory drugs
url https://doi.org/10.1038/s41598-022-19583-w
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