Gingival Fibroblasts-mediated Pathophysiology of Periodontal Diseases, Periodontitis and Drug-induced Gingival Overgrowth

Drug-induced gingival overgrowth is a side effect associated with 3 types of drugs: anticonvulsants (phenytoin), immunosuppressive agents (cyclosporine A), and various calcium channel blockers for cardiovascular diseases. Gingival overgrowth is characterized by the accumulation of extracellular matrix in gingival connective tissues, particularly collagenous components with various degrees of inflammation. Although the mechanisms of these disorders have not been elucidated, recent studies suggest that these disorders seem to be induced by the disruption of homeostasis of collagen synthesis and degradation in gingival connective tissue, predominantly through the inhibition of collagen phagocytosis of gingival fibroblasts. In this review, we focus on collagen metabolism in drug-induced gingival overgrowth, focusing on the regulation of collagen phagocytosis in fibroblasts. DOI: 10.3329/bjpp.v25i1.5743Bangladesh J Physiol Pharmacol 2009; 25(1&2) : 26-29

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Drug-induced gingival hyperplasia: An in vitro study using amlodipine and human gingival fibroblasts

International Journal of Immunopathology and Pharmacology ◽

10.1177/2058738419827746 ◽

2019 ◽

Vol 33 ◽

pp. 205873841982774 ◽

Cited By ~ 1

Author(s):

Dorina Lauritano ◽

Marcella Martinelli ◽

Alessandro Baj ◽

Giada Beltramini ◽

Valentina Candotto ◽

...

Keyword(s):

Gene Expression ◽

Inflammatory Responses ◽

Human Gingival Fibroblasts ◽

Gingival Tissue ◽

Gingival Fibroblast ◽

Gingival Hyperplasia ◽

Gingival Fibroblasts ◽

Drug Induced ◽

Gingival Overgrowth

Gingival overgrowth is a serious side effect that accompanies the use of amlodipine. Several conflicting theories have been proposed to explain the fibroblast’s function in gingival overgrowth. To determine whether amlodipine alters the inflammatory responses, we investigated its effects on gingival fibroblast gene expression as compared with untreated cells. Fragments of gingival tissue of healthy volunteers (11 years old boy, 68 years old woman, and 20 years old men) were collected during operation. Gene expression of 29 genes was investigated in gingival fibroblast cell culture treated with amlodipine, compared with untreated cells. Among the studied genes, only 15 ( CCL1, CCL2D, CCL5, CCL8, CXCL5, CXCL10, CCR1, CCR10, IL1A, IL1B, IL5, IL7, IL8, SPP1, and TNFSF10) were significantly deregulated. In particular, the most evident overexpressed genes in treated cells were CCR10 and IL1A. These results seem to indicate a possible role of amlodipine in the inflammatory response of treated human gingival fibroblasts.

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Drug-Induced Gingival Overgrowth: The Effect of Cyclosporin A and Mycophenolate Mophetil on Human Gingival Fibroblasts

Biomedicines ◽

10.3390/biomedicines8070221 ◽

2020 ◽

Vol 8 (7) ◽

pp. 221 ◽

Cited By ~ 1

Author(s):

Dorina Lauritano ◽

Giulia Moreo ◽

Luisa Limongelli ◽

Annalisa Palmieri ◽

Francesco Carinci

Keyword(s):

Extracellular Matrix ◽

Cell Viability ◽

Cyclosporin A ◽

Chronic Administration ◽

Immunosuppressive Drugs ◽

Matrix Metalloproteases ◽

Human Gingival Fibroblasts ◽

Gingival Fibroblasts ◽

Drug Induced ◽

Gingival Overgrowth

Drug-induced gingival overgrowth may occur after a chronic administration of three classes of systemic drugs: Anticonvulsants, immunosuppressants, and calcium channel blockers. This study aimed to investigate how cyclosporin A and mycophenolate mophetil (immunosuppressive drugs) could interfere with human gingival fibroblasts functions, leading to gingival enlargement. Human gingival fibroblasts derived from the tissue of a 60-year-old female were cultured in a DMEME medium. A stock solution with 1 mg/mL of mycophenolate and 1 mg/mL of cyclosporine were prepared and dissolved in a DMEM medium to prepare a serial dilution at the concentrations of 5000, 2000, 1000, 500, and 100 ng/mL, for both treatments. Cell viability was measured using the PrestoBlue™ Reagent Protocol. Quantitative real-time RT-PCR was performed in order to analyze the expression of 57 genes coding for gingival fibroblasts “Extracellular Matrix and Adhesion Molecules”. Mycophenolate and cyclosporine had no effect on fibroblast cell viability at 1000 ng/mL. Both the treatments showed similar effects on the expression profiling of treated cells: Downregulation of most extracellular matrix metalloproteases genes (MMP8, MMP11, MMP15, MMP16, MMP24) was assessed, while CDH1, ITGA2, ITGA7, LAMB3, MMP12, and MMP13 were recorded to be upregulated in fibroblasts treated with immunosuppressive drugs. It has been demonstrated that gingival overgrowth can be caused by the chronic administration of cyclosporin A and mycophenolate mophetil. However, given the contrasting data of literature, further investigations are needed, making clear the possible effects of immunosuppressive drugs on fibroblasts.

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Connective Tissue Metabolism and Gingival Overgrowth

Critical Reviews in Oral Biology & Medicine ◽

10.1177/154411130401500305 ◽

2004 ◽

Vol 15 (3) ◽

pp. 165-175 ◽

Cited By ~ 91

Author(s):

P. C. Trackman ◽

A. Kantarci

Keyword(s):

Extracellular Matrix ◽

Connective Tissue ◽

Oral Hygiene ◽

Tissue Specificity ◽

Gingival Fibroblast ◽

Drug Induced ◽

Gingival Overgrowth ◽

Connective Tissue Metabolism ◽

Matrix Metabolism ◽

Systemic Health

Gingival overgrowth occurs mainly as a result of certain anti-seizure, immunosuppressive, or antihypertensive drug therapies. Excess gingival tissues impede oral function and are disfiguring. Effective oral hygiene is compromised in the presence of gingival overgrowth, and it is now recognized that this may have negative implications for the systemic health of affected patients. Recent studies indicate that cytokine balances are abnormal in drug-induced forms of gingival overgrowth. Data supporting molecular and cellular characteristics that distinguish different forms of gingival overgrowth are summarized, and aspects of gingival fibroblast extracellular matrix metabolism that are unique to gingival tissues and cells are reviewed. Abnormal cytokine balances derived principally from lymphocytes and macrophages, and unique aspects of gingival extracellular matrix metabolism, are elements of a working model presented to facilitate our gaining a better understanding of mechanisms and of the tissue specificity of gingival overgrowth.

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Disposition of nifedipine in plasma and gingival crevicular fluid in relation to drug-induced gingival overgrowth

Journal of Periodontal Research ◽

10.1111/j.1600-0765.1993.tb01081.x ◽

1993 ◽

Vol 28 (5) ◽

pp. 373-378 ◽

Cited By ~ 28

Author(s):

J. S. Ellis ◽

R. A. Seymour ◽

S. Monkman ◽

J. R. Idle

Keyword(s):

Gingival Crevicular Fluid ◽

Drug Induced ◽

Gingival Overgrowth ◽

Crevicular Fluid

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Drug-Induced Gingival Overgrowth in an 8-Year-Old Girl: A Case Report

Avicenna Journal of Dental Research ◽

10.34172/ajdr.2021.21 ◽

2021 ◽

Vol 13 (3) ◽

pp. 109-112

Author(s):

Parviz Torkzaban ◽

Amir Talaie

Keyword(s):

Systemic Lupus Erythematosus ◽

Case Report ◽

Autoimmune Disease ◽

Lupus Erythematosus ◽

Immunological Tolerance ◽

Systemic Autoimmune Disease ◽

Channel Blockers ◽

Systemic Lupus ◽

Drug Induced ◽

Gingival Overgrowth

Systemic lupus erythematosus is a systemic autoimmune disease that involves multi organs. Genetic, endocrine, immunological, and environmental factors influence the loss of immunological tolerance against self-antigens leading to the formation of pathogenic autoantibodies that cause tissue damage through multiple mechanisms. The gingival overgrowth can be caused by three factors: noninflammatory, hyperplastic reaction to the medication; chronic inflammatory hyperplasia; or a combined enlargement due to chronic inflammation and drug-induced hyperplasia. Drug-Induced Gingival Overgrowth is associated with the use of three major classes of drugs, namely anticonvulsants, calcium channel blockers, and immunosuppressants. Due to recent indications for these drugs, their use continues to grow.

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Oral Contraceptives Induced Gingival Overgrowth – A Clinical Case Report

POJ Dental and Oral Care ◽

10.32648/2578-8817/1/1/001 ◽

2017 ◽

Vol 1 (1) ◽

pp. 1-5

Author(s):

Anushi Mahajan ◽

Ritesh Sood

Keyword(s):

Oral Contraceptives ◽

Oral Hygiene ◽

Periodontal Therapy ◽

Response To Therapy ◽

Drug Induced ◽

Gingival Overgrowth ◽

Periodontal Tissues ◽

Hygiene Measures ◽

Nonsurgical Periodontal Therapy ◽

Gingival Enlargement

Aim: The purpose of this article is to report a case of drug induced gingival enlargement due to oral contraceptives, managed by nonsurgical periodontal therapy. Background: Drug-induced gingival overgrowth remains the most widespread unwanted effect of systemic medication on the periodontal tissues. Hormones are specific regulatory molecules that modulate a host of body functions. Oral contraceptives that contain estrogen and/or progesterone are associated with gingival enlargement. Report: A 32-year-old female presented with a complaint of swelling of the gingiva with spontaneous bleeding in the mandibular anterior region for a period of two years. The health history documented the use of contraceptives for two years, and a clinical examination revealed the existence of poor oral hygiene and enlarged painful gingival tissues that bled when touched. Summary: Females on oral contraceptives can be considered as a “risk group” for periodontal diseases. Not all females on oral contraceptives respond in similar way. Plaque control is the most important procedure in periodontal therapy. Although the initial picture presented the possibility of surgical intervention, the clinical problems were resolved with non-surgical treatment. Another factor contributing to response to therapy is patient compliance. The patient followed home care instructions well and was effective in personal oral hygiene measures. Keywords: Gingival enlargement, Sex hormones, Oral contraceptives.

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A Case Report of a Gingival Plasma Cell Granuloma in a Patient on Antihypertensive Therapy: Diagnostic Enigma

Frontiers in Dentistry ◽

10.18502/fid.v16i2.1366 ◽

2019 ◽

Author(s):

Ruchi Gulati ◽

Madhu Singh Ratre ◽

Shaleen Khetarpal ◽

Manish Varma

Keyword(s):

Plasma Cell ◽

Plasma Cells ◽

Present Report ◽

Plasma Cell Granuloma ◽

Provisional Diagnosis ◽

Unique Case ◽

Drug Induced ◽

Gingival Overgrowth ◽

Neoplastic Lesion ◽

Patient Reported

The aim of the present report was to discuss a unique case of gingival plasma cell granuloma (PCG) in a hypertensive patient on Amlodipine therapy. Also, we attempt to emphasize the importance of considering primary and advance investigations before making a definite diagnosis. PCG is an extremely rare, reactive, non-neoplastic lesion characterized by the predominance of polyclonal plasma cells. Drug-induced gingival overgrowth is a known side effect of Amlodipine. A hypertensive 60-year-old female patient reported with a chief complaint of swollen gums and discomfort in the upper front teeth region. A provisional diagnosis of Amlodipine-induced gingival overgrowth, combined gingival overgrowth, and fibroma was suggested. Surprisingly, histopathology revealed it to be a plasma cell lesion which was confirmed by advanced investigations, thereby establishing a confirmatory diagnosis of PCG

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