Abstract
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.
Highlights
Gingival fibromatosis can be defined as a pathological diffused or local growth of marginal and attached gingiva or interdental papilla [1].Gingival overgrowth (GO) may cause severe consequences for the dento-maxillary apparatus: Inflammatory reaction may aggravate the periodontal condition, leading to tooth loss, while speechBiomedicines 2020, 8, 221; doi:10.3390/biomedicines8070221 www.mdpi.com/journal/biomedicinesBiomedicines 2020, 8, 221 capacity, chewing, and aesthetic may be altered [2,3]
In order to evaluate the effects induced by cyclosporine and mycophenolate, 57 genes belonging to the “Extracellular Matrix and Adhesion Molecules” pathway were amplified in fibroblasts after
Following the treatment for 24 h, both substances induced overexpression of the same genes in fibroblasts, including the adhesion molecules CDH1 and genes involved in the deposition of the extracellular matrix such as ITGA2, ITGA7, LAMB3, MMP12, and MMP13
Summary
Gingival fibromatosis ( called gingival overgrowth or hyperplasia) can be defined as a pathological diffused or local growth of marginal and attached gingiva or interdental papilla [1].Gingival overgrowth (GO) may cause severe consequences for the dento-maxillary apparatus: Inflammatory reaction may aggravate the periodontal condition, leading to tooth loss, while speechBiomedicines 2020, 8, 221; doi:10.3390/biomedicines8070221 www.mdpi.com/journal/biomedicinesBiomedicines 2020, 8, 221 capacity, chewing, and aesthetic may be altered [2,3]. Gingival overgrowth (GO) may cause severe consequences for the dento-maxillary apparatus: Inflammatory reaction may aggravate the periodontal condition, leading to tooth loss, while speech. The ethiopathogenetic mechanisms may derive from idiopathic, hereditary, or drug-induced forms [1]. Drug-induced GO is a side-effect, which may occur after the administration of certain systemic drugs, whose target organ is not the gingival tissue [4]. In particular, it could manifest itself as a result of chronic usage of three main classes of drugs: Anticonvulsants, immunosuppressants, and calcium channel blockers [8]. A study by Hatahira et al (2017) [9] reported that more than 70% of GO incidence was associated with cyclosporine (immunosuppressant) administration, while nifedipine (calcium channel blocker) and phenytoin (anticonvulsant) administration cause GO in 6–15% and 50% of individuals, respectively.
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