On the cellular and molecular mechanisms of drug-induced gingival overgrowth

Introduction:Gingival overgrowth has been linked to multiple factors such as adverse drug effects, inflammation, neoplastic processes, and hereditary gingival fibromatosis. Drug-induced gingival overgrowth is a well-established adverse event. In early stages, this gingival enlargement is usually loc...

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Autores: Ramírez Rámiz, Albert, Brunet i Llobet, Lluís, Lahor i Soler, Eduard, Miranda i Rius, Jaume
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2017
País:España
Institución:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/189712
Acceso en línea:https://hdl.handle.net/2445/189712
Access Level:acceso abierto
Palabra clave:Malalties de les genives
Fibroblasts
Col·lagen
Factors de creixement
Gum diseases
Collagen
Growth factors
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spelling On the cellular and molecular mechanisms of drug-induced gingival overgrowthRamírez Rámiz, AlbertBrunet i Llobet, LluísLahor i Soler, EduardMiranda i Rius, JaumeMalalties de les genivesFibroblastsCol·lagenFactors de creixementGum diseasesFibroblastsCollagenGrowth factorsIntroduction:Gingival overgrowth has been linked to multiple factors such as adverse drug effects, inflammation, neoplastic processes, and hereditary gingival fibromatosis. Drug-induced gingival overgrowth is a well-established adverse event. In early stages, this gingival enlargement is usually located in the area of the interdental papilla. Histologically, there is an increase in the different components of the extracellular matrix.Objective:The aim of this manuscript is to describe and analyze the different cellular and molecular agents involved in the pathogenesis of Drug-induced gingival overgrowth.Method:A literature search of the MEDLINE/PubMed database was conducted to identify the mechanisms involved in the process of druginduced gingival overgrowth, with the assistance of a research librarian. We present several causal hypotheses and discuss the advances in the understanding of the mechanisms that trigger this gingival alteration.Results:In vitro studies have revealed phenotypic cellular changes in keratinocytes and fibroblasts and an increase of the extracellular matrix with collagen and glycosaminoglycans. Drug-induced gingival overgrowth confirms the key role of collagenase and integrins, membrane receptors present in the fibroblasts, due to their involvement in the catabolism of collagen. The three drug categories implicated: calcineuron inhibitors (immunosuppressant drugs), calcium channel blocking agents and anticonvulsant drugs appear to present a multifactorial pathogenesis with a common molecular action: the blockage of the cell membrane in the Ca2+/Na+ ion flow. The alteration of the uptake of cellular folic acid, which depends on the regulated channels of active cationic transport and on passive diffusion, results in a dysfunctional degradation of the connective tissue. Certain intermediate molecules such as cytokines and prostaglandins play a role in this pathological mechanism. The concomitant inflammatory factor encourages the appearance of fibroblasts, which leads to gingival fibrosis. Susceptibility to gingival overgrowth in some fibroblast subpopulations is due to phenotypic variability and genetic polymorphism, as shown by the increase in the synthesis of molecules related to the response of the gingival tissue to inducing drugs. The authors present a diagram depicting various mechanisms involved in the pathogenesis of drug-induced gingival overgrowth.Conclusion:Individual predisposition, tissue inflammation, and molecular changes in response to the inducing drug favor the clinical manifestation of gingival overgrowth.Bentham Open2017info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/2445/189712Articles publicats en revistes (Odontoestomatologia)reponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglésReproducció del document publicat a: https://doi.org/10.2174/1874210601711010420The Open Dentistry Journal, 2017, vol. 11, p. 420-435https://doi.org/10.2174/1874210601711010420cc-by (c) Ramírez Rámiz, Albert et al., 2017https://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/1897122026-05-27T06:46:51Z
dc.title.none.fl_str_mv On the cellular and molecular mechanisms of drug-induced gingival overgrowth
title On the cellular and molecular mechanisms of drug-induced gingival overgrowth
spellingShingle On the cellular and molecular mechanisms of drug-induced gingival overgrowth
Ramírez Rámiz, Albert
Malalties de les genives
Fibroblasts
Col·lagen
Factors de creixement
Gum diseases
Fibroblasts
Collagen
Growth factors
title_short On the cellular and molecular mechanisms of drug-induced gingival overgrowth
title_full On the cellular and molecular mechanisms of drug-induced gingival overgrowth
title_fullStr On the cellular and molecular mechanisms of drug-induced gingival overgrowth
title_full_unstemmed On the cellular and molecular mechanisms of drug-induced gingival overgrowth
title_sort On the cellular and molecular mechanisms of drug-induced gingival overgrowth
dc.creator.none.fl_str_mv Ramírez Rámiz, Albert
Brunet i Llobet, Lluís
Lahor i Soler, Eduard
Miranda i Rius, Jaume
author Ramírez Rámiz, Albert
author_facet Ramírez Rámiz, Albert
Brunet i Llobet, Lluís
Lahor i Soler, Eduard
Miranda i Rius, Jaume
author_role author
author2 Brunet i Llobet, Lluís
Lahor i Soler, Eduard
Miranda i Rius, Jaume
author2_role author
author
author
dc.subject.none.fl_str_mv Malalties de les genives
Fibroblasts
Col·lagen
Factors de creixement
Gum diseases
Fibroblasts
Collagen
Growth factors
topic Malalties de les genives
Fibroblasts
Col·lagen
Factors de creixement
Gum diseases
Fibroblasts
Collagen
Growth factors
description Introduction:Gingival overgrowth has been linked to multiple factors such as adverse drug effects, inflammation, neoplastic processes, and hereditary gingival fibromatosis. Drug-induced gingival overgrowth is a well-established adverse event. In early stages, this gingival enlargement is usually located in the area of the interdental papilla. Histologically, there is an increase in the different components of the extracellular matrix.Objective:The aim of this manuscript is to describe and analyze the different cellular and molecular agents involved in the pathogenesis of Drug-induced gingival overgrowth.Method:A literature search of the MEDLINE/PubMed database was conducted to identify the mechanisms involved in the process of druginduced gingival overgrowth, with the assistance of a research librarian. We present several causal hypotheses and discuss the advances in the understanding of the mechanisms that trigger this gingival alteration.Results:In vitro studies have revealed phenotypic cellular changes in keratinocytes and fibroblasts and an increase of the extracellular matrix with collagen and glycosaminoglycans. Drug-induced gingival overgrowth confirms the key role of collagenase and integrins, membrane receptors present in the fibroblasts, due to their involvement in the catabolism of collagen. The three drug categories implicated: calcineuron inhibitors (immunosuppressant drugs), calcium channel blocking agents and anticonvulsant drugs appear to present a multifactorial pathogenesis with a common molecular action: the blockage of the cell membrane in the Ca2+/Na+ ion flow. The alteration of the uptake of cellular folic acid, which depends on the regulated channels of active cationic transport and on passive diffusion, results in a dysfunctional degradation of the connective tissue. Certain intermediate molecules such as cytokines and prostaglandins play a role in this pathological mechanism. The concomitant inflammatory factor encourages the appearance of fibroblasts, which leads to gingival fibrosis. Susceptibility to gingival overgrowth in some fibroblast subpopulations is due to phenotypic variability and genetic polymorphism, as shown by the increase in the synthesis of molecules related to the response of the gingival tissue to inducing drugs. The authors present a diagram depicting various mechanisms involved in the pathogenesis of drug-induced gingival overgrowth.Conclusion:Individual predisposition, tissue inflammation, and molecular changes in response to the inducing drug favor the clinical manifestation of gingival overgrowth.
publishDate 2017
dc.date.none.fl_str_mv 2017
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/189712
url https://hdl.handle.net/2445/189712
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: https://doi.org/10.2174/1874210601711010420
The Open Dentistry Journal, 2017, vol. 11, p. 420-435
https://doi.org/10.2174/1874210601711010420
dc.rights.none.fl_str_mv cc-by (c) Ramírez Rámiz, Albert et al., 2017
https://creativecommons.org/licenses/by/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc-by (c) Ramírez Rámiz, Albert et al., 2017
https://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Bentham Open
publisher.none.fl_str_mv Bentham Open
dc.source.none.fl_str_mv Articles publicats en revistes (Odontoestomatologia)
reponame:Dipòsit Digital de la UB
instname:Universidad de Barcelona
instname_str Universidad de Barcelona
reponame_str Dipòsit Digital de la UB
collection Dipòsit Digital de la UB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,198674

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