Role of transforming growth factor beta-connective tissue growth factor pathway in dihydropyridine calcium channel blockers-induced gingival overgrowth

Vol. 55 No. 2 Suppl., 2014
This supplement was not sponsored by Outside Organizations.


Catalina Gabriela Pisoschi, Camelia Elena Stanciulescu, Ana Marina Andrei, Anca Berbecaru-Iovan, Cristina Munteanu, Florica Popescu, Ileana Monica Banita

Background: Gingival overgrowth was reported as a side effect after chronic administration of several drugs, which, despite their different pharmacological effect, seem to have the gingival mucosa as a secondary target. The thickness of the gingival epithelium and fibrosis in the lamina propria are unspecific changes that together determine the enlargement of the gingival mucosa, but the molecular mechanisms responsible for the imbalance of collagen synthesis/breakdown are still uncertain. The aim of our study was to assess the role of TGF-beta1-CTGF pathway in the activation of cells with a fibrilogenetic phenotype responsible for the gingival fibrosis developed after chronic administration of dihydropyridine calcium channel blockers. Materials and Methods: Fragments of gingival tissue collected from patients clinically diagnosed with gingival overgrowth after chronic administration of nifedipine and amlodipine were processed for paraffin embedding. Serial sections were used for routine staining Masson and Gomori silver impregnation in order to reveal collagen accumulation and for immunohistochemical reactions to label TGF-beta1, CTGF, Ki67 and alpha-SMA. Results: Routine histological staining for collagen revealed the presence of gingival fibrosis and a change between type I collagen/type III collagen ratio. Regardless of the drug involved, many slides showed extended TGF-beta1 positive areas, mainly in the profound - spinous and basal - layers, but also in some cells from the subjacent connective tissue. CTGF exposed intense positive reaction in the basal and parabasal layers, but also in resident cells from the connective tissue. Ki67 immunolabeling did not reveal an increased fibroblast proliferation in the lamina propria. We noticed the presence of a small number of myofibroblasts in the lamina propria. Conclusions: These findings suggest that TGF-beta1-CTGF axis is activated in dihydropyridine calcium channel blockers-induced gingival overgrowth and exerts a different control on the activation of fibroblasts with a synthetic phenotype. These results also have implications for better understanding mechanisms of fibrosis and the future use of this pathogenic pathway as a therapeutic target in order to limit gingival fibrosis.

Corresponding author: Camelia Elena Stanciulescu, Lecturer, Pharm, PhD; e-mail:

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Georgeta Voicu, Adrian Gabriel Anghel, Mihaela Badea, Emanoil Bordei, Georgiana Crantea, Raluca Ionela Gavrila, Alexandru Grecu, Denisa Ana-Maria Jercan, Bogdan Cristian Nicolae, Greta Cristina Vochitoaia, Kuete Tchinda, Alina Maria Holban, Coralia Bleotu, Alexandru Mihai Grumezescu

This paper reports the potential of silica network to sensitize tumor cells and stimulate antitumor toxicity of fludarabine (FLU) and paclitaxel (PAC) against HCT8 cells. SiO2, SiO2/FLU and SiO2/PAC nanostructured materials were characterized by X-Ray Diffraction, Scanning Electron Microscopy, InfraRed Microscopy and in vitro biological assays. When using SiO2/PAC, it can be observed that the cytostatic effect of PAC is boosted only at high concentrations of this material. On the other hand, in the case of SiO2/FLU, data showed an enhancement in the cytostatic activity of FLU by up to 25%, also when using this nanomaterial in low doses. These data represent preliminary study on the impact on silica nano-networks in targeted delivery and controlled release of antitumor drugs and they may be efficiently used for future biomedical applications in cancer therapy.

Corresponding author: Alexandru Mihai Grumezescu, Chem. Eng., PhD; e-mail:

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