Role of myofibroblasts in normal and pathological periodontal wound healing.

Myofibroblasts represent specific subpopulations of cells with important roles in tissue remodeling in both health and disease. They are not usually found in resting healthy tissues. However, they increase in number during the proliferative phase of wound healing. In these conditions, myofibroblasts secrete and organize different molecular components of the extracellular matrix that with time will reconstitute and hopefully regenerate the damaged tissue. Importantly, these cell populations must be eliminated after wound healing has been completed. However, deficiencies in their differentiation or the persistence of this cell population has been associated with the development of delayed wound healing and fibrosis, respectively. In the present review, we analyze the involvement of myofibroblasts in periodontal wound healing and their potential contribution to tissue homeostasis and disease.

Phenytoin-induced gingival overgrowth.

Gingival overgrowth is a common adverse effect of therapy with Phenytoin, having important medical and cosmetic implications. Poor periodontal hygiene is an important risk factor for severity of Phenytoin-induced gingival overgrowth (PIGO), which is a time-dependent process. There is complex interplay of altered fibroblast biology, connective tissue turnover, inflammatory processes, and growth factors on a background of genetic susceptibility to produce increase in various components of interstitial matrix in PIGO tissue. Treatment options have included change of PHT to another anti-seizure drug, measures to improve periodontal hygiene and gingivectomy. There is conclusive evidence that folic acid supplementation significantly decreases the incidence of PIGO.

The upregulation of heat shock protein 47 in human gingival fibroblasts stimulated with cyclosporine A.

BACKGROUND AND OBJECTIVE: Heat shock protein 47 (Hsp47), a collagen-specific molecular chaperone, is involved in the processing and/or secretion of procollagen. Heat shock protein 47 is consistently and dramatically upregulated in a variety of fibrotic diseases. The aim of this study was to compare Hsp47 expression in normal gingival tissues and cyclosporine A-induced gingival overgrowth specimens and further explore the potential mechanisms that may lead to induction of Hsp47 expression. MATERIAL AND METHODS: Fifteen cyclosporine A-induced gingival overgrowth specimens and five normal gingival tissues were examined by immunohistochemistry. Western blot was used to investigate the effects of cyclosporine A on the expression of Hsp47 in human gingival fibroblasts. In addition, Aggregatibacter actinomycetemcomitans, interleukin-1 alpha (IL-1 alpha) and mitogen-activated protein kinase kinase (MEK) inhibitor U0126 were added to seek the possible regulatory mechanisms of Hsp47 expression. RESULTS: A significantly higher percentage of cells positively stained for Hsp47 was noted in the cyclosporine A-induced gingival overgrowth group than in the normal gingival group (p < 0.05). Expression of Hsp47 was observed mainly in the cytoplasm of fibroblasts, endothelial cells, epithelial cells and inflammatory cells. Expression of Hsp47 was significantly higher in cyclosporine A-induced gingival overgrowth specimens with higher levels of inflammatory infiltrates (p < 0.05). Cyclosporine A upregulated Hsp47 expression in human gingival fibroblasts in a dose-dependent manner (p < 0.05). The addition of A. actinomycetemcomitans or interleukin-1 alpha significantly increased Hsp47 expression compared with cyclosporine A alone (p < 0.05). The MEK inhibitor U0126 was found to inhibit cyclosporine A-induced Hsp47 expression (p < 0.05). CONCLUSION: Expression of Hsp47 is significantly upregulated in cyclosporine A-induced gingival overgrowth specimens, and Hsp47 expression induced by cyclosporine A in fibroblasts may be mediated by the MEK signal transduction pathway. The expression of Hsp47 could be significantly enhanced by A. actinomycetemcomitans and interleukin-1 alpha.

Clinical, imaging and histopathological correlations of gingival overgrowth: a retrospective analysis in northeastern Romanian population.

BACKGROUND: Gingival overgrowth refers to an increase in the size of the gingival tissue. The etiology varies, and is often a multi-factor issue; what may contribute to gingival enlargement are aspects, such as disease, local and systemic conditions and idiopathic factors. The aim of the present study is to analyze and to correlate the clinical, epidemiological, imaging and histopathological (HP) features of gingival overgrowth in northeastern Romanian population. PATIENTS, MATERIALS AND METHODS: We conducted a clinical, imaging, and pathological study on 98 patients with gingival overgrowth, who underwent a surgical intervention for a gingival biopsy in the Office of Oral and Maxillofacial Surgery, "Prof. Dr. Nicolae Oblu" Emergency Clinical Hospital, Iasi, Romania, during a 14-month period (January 1, 2018 to February 28, 2019). All patients with localized gingival overgrowth had clinical and imaging investigations done and then were referred to an oral and maxillofacial facility. A surgeon performed the excision of the gingival overgrowth and then sent the surgical specimens to the Laboratory of Pathology for HP examination. RESULTS: Local inflammation was found responsible for the gingival overgrowth in most of the cases, with the number of females outnumbering that of the males. A very good correlation was found between clinical and HP diagnosis when epithelial hyperplasia, peripheral giant cell granuloma and pyogenic granuloma were involved and a moderate one when fibrous hyperplasia was involved. CONCLUSIONS: These findings suggest that the occurrence of gingival overgrowth can have many causes, which highlights the importance of clinical pathology in assisting practitioners with making a better diagnosis.

The effect of basic fibroblast growth factor on cell cycle in human gingival fibroblasts from nifedipine responder and non-responder.

It has previously been demonstrated that gingival fibroblasts derived from nifedipine-reactive patients (nifedipine responders) show a greater cell proliferation rate than those from nifedipine non-reactive patients (nifedipine non-responders) in the presence of 1 microM nifedipine. The aim of the present study was to characterize cell cycle differences between nifedipine responder and non-responder fibroblast cells and determine the effect of basic fibroblast growth factor (bFGF) on cell cycle progression. Further, the effect of bFGF on cyclins A, B1, D1, E, and CDKs 1, 2, 4, 6 mRNA expression in responder and non-responder cells was investigated. A population of nifedipine responder cells underwent progression to S and G2/M phases from G0/G1 phase in the presence of 10% fetal calf serum or 10 ng/ml bFGF was greater than nifedipine non-responder cells. mRNA expression of cyclins A, B1, D1, E and CDKs 1, 2, 4, 6 in the presence of 10 ng/ml bFGF was generally greater in nifedipine responder cells than non-responder cells. These results indicate that nifedipine responder cells may be more susceptible to growth factors such as bFGF with a resultant increase in expression of cyclins and CDKs in responder compared with non-responder cells.

[An increase in gingival volume induced by drugs (phenytoin, cyclosporine and calcium antagonists). A review of the literature]. / Aumento di volume gengivale indotto da farmaci (fenitoina, ciclosporina, e calcioantagonisti). Revisione della letteratura.

The aim of this review is to evaluate the side effects of some drug therapies on the gingival tissue in certain susceptible individuals. Phenytoin, cyclosporine-A and a variety of calcium channel blockers have been shown to produce gingival overgrowth. In this paper the pharmacodynamics and pharmacokinetics of these drugs, the pathogenesis, the clinical aspect of the enlargement and its treatment are examined. Several of the reviewed theories on pathogenesis are well documented in the literature, while others are controversial and less described. The old term gingival hyperplasia is not exact because histologically an increase in the number of fibroblasts has not been demonstrated, but an increase has been found out in the amount of collagen fibers and noncollagenous proteins in the connective tissue. The clinical findings have the same characteristics both in location and growth pattern while prevention is primarily directed at the removal of local irritant factors. The prevalence and severity of gingival enlargement increase in heart transplant patients who are often medicated with cyclosporin and channel blockers.

Hormonal factors in periodontal disease.

This article discusses the effects of sex steroid hormones, glucocorticoids and insulin deficiency on periodontal tissues, and the possible consequences on periodontal disease progression. The androgens and oestrogens have predominantly anabolic functions in stimulating matrix synthesis, which is applicable to periodontal repair and medication-induced gingival overgrowth. Oestrogen and progesterone can contribute to pregnancy gingivitis; long-term use of hormonal contraceptives can accelerate progression of periodontal disease. Higher levels of circulating cortisol, associated with stress, can influence the onset of acute necrotic ulcerative gingivitis. Gingivitis and periodontal disease are reported to be more prevalent in type 1 and type 2 diabetes mellitus (periodontal disease, particularly in older, less well controlled subjects) than in non-diabetic individuals.

Risk factors for drug-induced gingival overgrowth.

BACKGROUND/AIMS: Drug-induced gingival overgrowth remains a significant problem for the periodontologist. Many patients medicated with the drugs implicated in this unwanted effect experience significant, recurrent gingival problems that require repeated surgical excisions. In this review, we attempt to identify and quantify the various "risk factors" associated with both the development and expression of the drug-induced gingival changes. METHOD: The risk factors appraised include age, sex, drug variables, concomitant medication, periodontal variables and genetic factors. Elucidation of such factors may help to identify "at risk patients" and then develop appropriate treatment strategies. RESULTS: Of the factors identified, the only one that can be affected by the periodontologist is the patents' periodontal condition. However, drug variables and concomitant medication do impact upon the expression of gingival overgrowth. CONCLUSION: The identification of risk factors associated with both the prevalence and severity of drug-induced gingival overgrowth is important for all parties involved with this unwanted effect. Both periodontologist and patient have an important rôle to play in improving oral hygiene and gingival health. Likewise, there is always an opportunity to establish a close liaison between the patient's physician and the periodontologist to try and identify alternative drug regimens that can help reduce the impact of this unwanted effect.

The rôle of time in reducing gingival overgrowth in heart-transplanted patients following cyclosporin therapy.

BACKGROUND, AIMS: In a previous cross-sectional study, the relevant rôle of time in reducing gingival overgrowth (GO) in heart-transplanted patients undergoing Cyclosporin A (CsA) therapy was hypothesized to explain the inverse relationship between GO and months since the graft. METHODS: In the present study, the relationship between GO and time was investigated prospectively in a group of 21 heart transplanted patients who have been regularly followed up to 48 months. RESULTS: 6 months after beginning CsA therapy (1st appointment), 7 out of 21 patients (33%) had clinical GO as confirmed by a hyperplastic index (HI) >30. There was no significant difference between these values with respect to those detected during the 2nd appointment at 9 months. At this time, all patients underwent a regular oral hygiene program. Gingival and plaque indices significantly decreased at the 3rd appointment (12 months) both in the group of responders and in the group of non-responders and remained significantly unchanged with time; HI significantly decreased with time only in the group of responders, the decrease becoming significant 36 months after heart transplantation. As a consequence, the number of responders decreased from 7 at the 1st appointment to 5 after 12 months, 4 after 24 months, 2 after 36 months following heart transplantation. CONCLUSION: The results suggest that GO necessarily develops in responders within 6 months from heart transplantation and in most subjects may be a time-related side-effect probably due to a progressive reduction in the sensitivity of the periodontum to CsA.