transforming-growth-factor-beta and Gingival-Hyperplasia

The present study examined histological difference between ossifying fibromas (OF, n=5) and peripheral cemento-ossifying fibromas (PCOF, n=7). Bone morphogenetic proteins (BMP)-2 and -4, osteopontin (OPN), osteocalcin (OCN) and proliferating cell nuclear antigen (PCNA) were used for the immunohistochemical examinations. Oxytalan fibers present at the periodontal tissue were stained to determine the tumor cell origin. Many OFs showed high immunohistochemical reactions for BMP-2, -4 and OPN compared to those of PCOFs. PCNA index (IP) of OFs was significantly higher than that of PCOFs. All the PCOFs showed a high expression of oxytalan fibers. Only two OFs exhibited a small number of oxytalan fibers. These results suggest that PCOF has only little ability to form hard tissue and seems to be a reactive lesion. The expression of oxytalan fibers reveals that OF does not only originate from periodontal tissue.

Topics: Adolescent; Adult; Bone Morphogenetic Protein 2; Bone Morphogenetic Protein 4; Bone Morphogenetic Proteins; Calcinosis; Child; Female; Fibroma, Ossifying; Gingival Hyperplasia; Gingival Neoplasms; Humans; Immunohistochemistry; Jaw Neoplasms; Male; Middle Aged; Osteocalcin; Osteopontin; Proliferating Cell Nuclear Antigen; Transforming Growth Factor beta

The mechanism underlying phenytoin (PHT)-induced gingival enlargement (GE) is not yet known. The aim of the present study was to investigate transforming growth factor-beta1 (TGF-beta1), platelet-derived growth factor-BB (PDGF-BB) and basic fibroblast growth factor (bFGF) profiles in the gingival crevice fluid (GCF) of patients with PHT-induced GE and to compare the results with healthy controls. Five PHT-treated patients and five healthy subjects with normal periodontal tissue were included in this study. GCF samples were collected from (i) enlarged gingival sites in patients receiving PHT (GE+); (ii) non-enlarged gingival sites in the same patients (GE-); (iii) normal gingival sites of healthy subjects (control). The levels of TGF-beta1, PDGF-BB and bFGF in the GCF samples were analysed by ELISA. The results showed that the total amounts of TGF-beta1 and PDGF-BB in the GE+ group were higher than in the GE- group and significantly higher than in the control group (P < 0.05). However, no significant differences were found between the groups when the concentrations of these growth factors were compared. bFGF levels were not compared as this growth factor could be detected in only 33, 41 and 44% of the GE+, GE- and control GCF samples, respectively. These results show that TGF-beta1 and PDGF-BB are readily detectable in GCF obtained from enlarged and non-enlarged sites of PHT recipients and suggest that since the amounts were markedly higher at the GE+ than the GE- sites, the systemic administration of PHT has a pronounced localised effect on the levels of these growth factors. Moreover, our findings provide evidence that both TGF-beta1 and PDGF-BB are closely associated with the clinical manifestation of PHT-induced GE.

Topics: Adolescent; Adult; Anticonvulsants; Becaplermin; Female; Fibroblast Growth Factor 2; Gingival Crevicular Fluid; Gingival Hyperplasia; Growth Substances; Humans; Male; Middle Aged; Phenytoin; Platelet-Derived Growth Factor; Proto-Oncogene Proteins c-sis; Transforming Growth Factor beta; Transforming Growth Factor beta1

Some drugs such as phenytoin, calcium blockers, or cyclosporins are known to cause gingival fibrous hyperplasia, an unwanted side effect. Decreased collagen catabolism in overgrown gingival tissue has been proposed as one of the reasons causing the disease. The effect of tranilast, which suppresses collagen synthesis and cell proliferation, on matrix metalloproteinase (MMP-1) secretion from human gingival fibroblast, was studied in vitro.. Human gingival fibroblasts were cultured from specimens taken from healthy, periodontal, and overgrown gingival tissues. The effects of tranilast on cell proliferation and MMP-1 secretion from gingival fibroblast were assessed. Inhibitory effect of transforming growth factor (TGF)-beta secretion from gingival fibroblast by tranilast was also evaluated.. Tranilast did not interfere with cell proliferation at the low concentrations. MMP-1 concentration significantly increased at the lower doses of tranilast up to about 2-fold compared to controls (P < 0.05). In contrast, higher doses of tranilast significantly decreased activity to 30% and 20%, respectively. MMP-1 secretion was inhibited significantly by phenytoin, nifedipine, and cyclosporin A and the depressed MMP-1 recovered to the control level with tranilast. The amount of secretion from normal and periodontitis gingival fibroblast specimens did not differ, but that from the overgrown gingiva was significantly less than the other types. Moreover, TGF-beta secretion was significantly inhibited by 300 microM of tranilast.. Tranilast upregulates the expression of type 1 collagenase suppressed by gingival overgrowth-inducing drugs, and inhibits TGF-beta secretion from gingival fibroblasts. Therefore, tranilast could be considered as an agent for controlling gingival over-growth.

Topics: Adult; Anti-Allergic Agents; Cells, Cultured; Collagen Type I; Fibroblasts; Gingiva; Gingival Hyperplasia; Humans; Matrix Metalloproteinase 1; Matrix Metalloproteinase Inhibitors; ortho-Aminobenzoates; Transforming Growth Factor beta; Up-Regulation

Although drug-induced gingival hyperplasia has been extensively studied, the pathogenesis of this disorder has not been clarified to date. Transforming growth factor beta (TGF beta) and basic fibroblast growth factor (bFGF) have been shown to be implicated in diverse fibrotic and hyperplastic diseases. Heparan sulphate proteoglycan (HSPG), which is composed of heparan sulphate glycosaminoglycan (HSGAG), has also been shown to play an important role in the pathogenesis of tissue overgrowth by enhancing the functions of bFGF. However, the possible implication of these growth factors in gingival hyperplasia has not been studied. Immunohistochemical localization of TGF beta, bFGF, their receptors and HSGAG was studied in 4 nifedipine-induced and 5 phenytoin-induced hyperplastic gingival tissues, and 5 non-hyperplastic control gingival tissues to elucidate the pathogenesis of this disease. Significant immunostaining against TGF beta, bFGF, the receptors of these two growth factors and HSGAG was observed in the lamina propria of hyperplastic gingival tissues while less immunostaining was observed in the controls. The mean numbers of immunostained cells against TGF beta, bFGF, their receptors in a square unit (0.1 x 0.1 mm) of the lamina propria, which were counted to 10 units of each hyperplastic gingival tissue, were significantly higher than those of the controls. The results suggest that the increased synthesis of TGF beta, bFGF, their receptors and HSGAG may be related to the pathogenesis of drug-induced gingival hyperplasia.

Topics: Adolescent; Adult; Aged; Anticonvulsants; Calcium Channel Blockers; Cell Count; Coloring Agents; Female; Fibroblast Growth Factor 2; Gingiva; Gingival Hyperplasia; Heparitin Sulfate; Humans; Immunohistochemistry; Male; Nifedipine; Phenytoin; Receptors, Fibroblast Growth Factor; Receptors, Growth Factor; Receptors, Transforming Growth Factor beta; Transforming Growth Factor beta

Immunohistochemical detection of bone morphogenetic protein (BMP) in calcifying fibrous epulis was performed to elucidate the biological process of ossification and cemento-ossification. In a total 25 cases, 15 (60%) showed positive BMP staining in bone forming areas. Histopathological features of developing hard tissues were varied, consisting of structures such as woven bone and cemento-osseous formations. BMP immunostaining was limited to osteoblasts and fibrous connective tissue surrounding the bone matrix. BMP was concentrated in the periodontal fibres and in dense fibrous structures in the cemento-osseous masses. On the basis of histopathological and immunohistochemical features, the histogenesis of ossifying and cemento-ossifying processes appear to be of two possible origins; the excessive proliferation of periodontal ligament and a metaplastic process occurring in the connective tissue fibres (non-periodontal in origin), with the former being more common.

Topics: Animals; Bone Morphogenetic Proteins; Calcinosis; Gingival Hyperplasia; Humans; Immunohistochemistry; Mice; Ossification, Heterotopic; Periodontal Ligament; Proteins; Transforming Growth Factor beta

Topics: Gene Expression; Gingival Hyperplasia; Growth Substances; Humans; Monocytes; Phenytoin; Platelet-Derived Growth Factor; Transforming Growth Factor beta