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Cited by 155Oral and gingival health researchOral Health Pathology and TreatmentOral and Maxillofacial Pathology

Molecular and Clinical Aspects of Drug-induced Gingival Overgrowth

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Trackman, P.C., Kantarci, A.·2015·Journal of Dental Research
DOI 10.1177/0022034515571265PMC PMC4485217
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Abstract

Drug-induced gingival overgrowth is a tissue-specific condition and is estimated to affect approximately one million North Americans. Lesions occur principally as side-effects from phenytoin, nifedipine, or ciclosporin therapy in approximately half of the people who take these agents. Due to new indications for these drugs, their use continues to grow. Here, we review the molecular and cellular characteristics of human gingival overgrowth lesions and highlight how they differ considerably as a function of the causative drug. Analyses of molecular signaling pathways in cultured human gingival fibroblasts have provided evidence for their unique aspects compared with fibroblasts from the lung and kidney. These findings provide insights into both the basis for tissue specificity and into possible therapeutic opportunities which are reviewed here. Although ciclosporin-induced gingival overgrowth lesions exhibit principally the presence of inflammation and little fibrosis, nifedipine- and especially phenytoin-induced lesions are highly fibrotic. The increased expression of markers of gingival fibrosis, particularly CCN2 [also known as connective tissue growth factor (CTGF)], markers of epithelial to mesenchymal transition, and more recently periostin and members of the lysyl oxidase family of enzymes have been documented in phenytoin or nifedipine lesions. Some oral fibrotic conditions such as leukoplakia and oral submucous fibrosis, after subsequent additional genetic damage, can develop into oral cancer. Since many pathways are shared, the study of gingival fibrosis and comparisons with characteristics and molecular drivers of oral cancer would likely enhance understandings and functional roles of molecular drivers of these oral pathologies.

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  • Gingival tissue is in a constant state of injury and repair, resulting in an increase in chemical mediators such as cytokines, chemokines and an abundance of inflammatory cells.

    “their Gingival tissue is in a constant state of injury and repair. This results in an increase in chemical mediators such as cytokines, chemokines and an abundance of inflammatory cells [28, 29].”

    From An Update on the Mechanisms of Phenytoin Induced Gingival Overgrowth (2019) · cites this paper as [29]

    The Introduction (page unavailable) describes inflammation and changes in inflammatory-cell populations in gingival tissue, particularly in drug-induced overgrowth. It does not say that gingival tissue is constantly undergoing injury and repair, or that this process increases cytokines, chemokines and inflammatory cells. (LLM, conf=0.83)

    Experimental — accuracy not yet measured

  • These organisms produce established dental plaque biofilms that aggravate the inflammatory process.

    “These organisms produce established dental plaque biofilms aggravating the inflammatory process [28, 29].”

    From An Update on the Mechanisms of Phenytoin Induced Gingival Overgrowth (2019) · cites this paper as [29]

    The Introduction discusses inflammation in drug-induced gingival overgrowth, but does not connect it to organisms producing dental plaque biofilms. Searches for plaque, biofilm, bacteria, and microbial causes found no passage in our copy addressing that relationship; page numbers were not available. (LLM, conf=0.73)

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Cited by

Sorted by citations

Authors
Trackman, P. C., & Kantarci, A.
Affiliations
  • Boston University (US)
  • Forsyth Institute, Department of Applied Oral Sciences, Center for Periodontology, Cambridge, MA, USA
ORCID
Trackman, P.C.
Venue
Journal of Dental Research
Publisher
SAGE Publications
Published
2015-02-13
Volume
94
Issue
4
Pages
540-546
ISSN
  • 0022-0345 (ISSN-L)
  • 1544-0591
DOI
10.1177/0022034515571265
PMC
PMC4485217
OpenAlex
W2163127301
Cited by
155
References
2
Citations by year
2026: 4 · 2025: 13 · 2024: 16 · 2023: 12 · 2022: 19 · 2021: 21 · 2020: 20 · 2019: 10 · 2018: 14 · 2017: 17 · 2016: 2 · 2015: 7
FWCI
2.61
Type
journal article
Language
en
Open access
Licence
journals.sagepub.com/page/policies/text-and-data-mining-license (tdm)
Locations
  • Journal of Dental Research (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health
  • National Institute of Dental and Craniofacial Research (R01DE011004)
Topics
  • Health Sciences › Health Professions › Pharmacy › Oral and gingival health research
  • Health Sciences › Dentistry › Periodontics › Oral Health Pathology and Treatment
  • Health Sciences › Dentistry › Oral Surgery › Oral and Maxillofacial Pathology
Keywords
drug-induced gingival hyperplasia, phenytoin, nifedipine, cyclosporine, gingival fibrosis, connective tissue growth factor, epithelial-mesenchymal transition, periostin, gingival fibroblasts, tissue specificity, oral cancer, leukoplakia, oral submucous fibrosis, molecular pathways
MeSH terms
Anticonvulsants, Calcium Channel Blockers, Fibroblasts, Humans, Immunosuppressive Agents, Molecular Biology, Signal Transduction, Gingival Overgrowth

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