The Open Dentistry Journal

ISSN: 1874-2106 ― Volume 14, 2020

On the Cellular and Molecular Mechanisms of Drug-Induced Gingival Overgrowth

Albert Ramírez-Rámiz1, Lluís Brunet-LLobet2, Eduard Lahor-Soler1, Jaume Miranda-Rius1, *
1 Department of Odontostomatology. Faculty of Medicine and Health Sciences. University of Barcelona, Barcelona, Spain.
2 Department of Dentistry. Hospital Universitari Sant Joan de Déu. University of Barcelona, Barcelona, Spain.



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.


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.


A literature search of the MEDLINE/PubMed database was conducted to identify the mechanisms involved in the process of drug-induced 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.


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.


Individual predisposition, tissue inflammation, and molecular changes in response to the inducing drug favor the clinical manifestation of gingival overgrowth.

Keywords: Fibroblast, Collagen, Drug-induced gingival overgrowth, Growth factor, Cellular cultures.

Article Information

Identifiers and Pagination:

Year: 2017
Volume: 11
First Page: 420
Last Page: 435
Publisher Id: TODENTJ-11-420
DOI: 10.2174/1874210601711010420

Article History:

Received Date: 16/03/2017
Revision Received Date: 03/05/2017
Acceptance Date: 05/06/2017
Electronic publication date: 31/07/2017
Collection year: 2017

© 2017 Ramírez-Rámiz et al.

open-access license: This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International Public License (CC-BY 4.0), a copy of which is available at: This license permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

* Address correspondence to this author at the Department of Odontostomatology, Faculty of Medicine and Health Sciences, University of Barcelona, Feixa Llarga, s/n, 08907 L’Hospitalet de Llobregat, Barcelona, Spain; Tel: +34 934 024 276; Fax: +34 934 035 558; E-mail:

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