Analysis of the citation impact of Brazilian researchers in oral pathology and oral medicine over two decades.

BACKGROUND: Brazilian Oral Pathology (OP) and Oral Medicine (OM) have gained significant international recognition. However, no study has yet evaluated the impact of citations in scientific publications. Therefore, this study aimed to analyze the impact of citations from Brazilian researchers in OP and OM over the last two decades. MATERIAL AND METHODS: This was a cross-sectional study involving 50 researchers linked to postgraduate programs in OP/OM. Data collected from each professional's Lattes curriculum included gender, academic affiliation, the corporate category of the institution, and location. The number of papers published and citations received between 2004 to 2013 and 2014 to 2023 was also collected from the Web of Science database. RESULTS: Most researchers were male (56%) and from public institutions (90%), mainly in the Southeast region (60%). Over two decades, they collectively published 8,033 scientific articles, with significant growth (p<0.001) from to 2004-2013 to 2014-2023. While the average citations per researcher did not differ significantly between 2004-2013 and 2014-2023 (p=0.538), there was a notable 67.67% increase in citations in the last decade. CONCLUSIONS: Brazilian researchers in the areas of OP and OM have demonstrated a significant academic impact over the past two decades, with a marked increase in publications and citations over the last ten years. This highlights the contribution of Brazilians to the global scientific community in these areas.

Teleconsultations in oral medicine: dentist perception during the COVID-19 pandemic in Brazil.

BACKGROUND: The aim of this study was to describe the perception of dentists from the North macroregion of Minas Gerais, Brazil, users of telediagnosis in Oral Medicine, during the COVID-19 pandemic. MATERIAL AND METHODS: This is a cross-sectional and descriptive study. Data collection was carried out online, between May and October 2022. The information was transferred to the Statistical Package for the Social Sciences for Windows (SPPS)® version 24. RESULTS: The sample consisted of 255 dentists, predominantly female. Regarding perception, a significant percentage (47.8%) of respondents agreed that they would like to use telediagnosis frequently, more than half (60.6%) agreed that the technology is easy to use, only a small percentage (8.8%) needed technical support to use it and almost half (48.2%) mentioned the desire to continue using it after the pandemic. When asked if patients felt confident and comfortable when passing on information, more than half disagreed or remained neutral (58.4%), a similar result was found in relation to confidence in the application of the instrument by professionals. CONCLUSIONS: It is concluded that, during the pandemic, telediagnosis in Oral Medicine was an easy and adequate tool. However, professionals must be trained and prepared to be comfortable and ready for use.

Adverse reactions to the injection of face and neck aesthetic filling materials: a systematic review.

BACKGROUND: Adverse reactions, caused during the inflammation and healing process, or even later, can be induced by the injection of dermal filler and can present a variety of clinical and histological characteristics. In this study we aimed to review the adverse reactions associated with the injection of aesthetic filling materials in the face and neck. MATERIAL AND METHODS: The review was reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist. Studies published that mentioned adverse reactions in patients with aesthetic filling materials in the face or neck were included. Risk of bias was assessed using the Joanna Briggs Institute appraisal tool. After a 2-step selection process, 74 studies were included: 51 case reports, 18 serial cases, and five cohorts. RESULTS: A total of 303 patients from 20 countries were assessed. Lesions were more prevalent in the lip (18%), nasolabial folds (13%), cheeks (13%), chin (10%), submental (8%), glabella (7%), and forehead (6%). Histopathological analysis revealed a foreign body granuloma in 87.1% of the patients, 3% inflammatory granuloma, 3% lipogranuloma, 2.3% xanthelasma-like reaction, 1% fibrotic reaction, 0.7% amorphous tissues, 0.7% xanthelasma, 0.3% sclerosing lipogranuloma, 0.3% siliconoma, and 0.3% foreign body granuloma with scleromyxedema. In addition, two patients displayed keratoacanthoma and two others displayed sarcoidosis after cutaneous filling. The most commonly used materials were silicone fillers (19.7%), hyaluronic acid (15.5%), and hydroxyethyl methacrylate/ethyl methacrylate suspended in hyaluronic acid acrylic hydrogel (5.6%). All patients were treated, and only 12 had prolonged complications. CONCLUSIONS: There is evidence that adverse reaction can be caused by different fillers in specific sites on the face. Although foreign body granuloma was the most common, other adverse lesions were diagnosed, exacerbating systemic diseases. In this way, we reinforce the importance of previous systemic evaluations and histopathological analyses for the correct diagnosis of lesions.

Oral findings in Williams-Beuren syndrome.

BACKGROUND: Williams-Beuren syndrome (WBS; OMIM #194050) is a developmental disorder characterized by congenital heart disease, intellectual disability, dysmorphic facial features and ophthalmologic abnormalities. Oral abnormalities are also described in clinical manifestations of the disease. This paper describes orofacial features in patients with WBS. MATERIAL AND METHODS: Seventeen patients with a confirmed molecular diagnosis of WBS were examined for oral abnormalities through clinical oral evaluations and panoramic radiography. RESULTS: Malocclusion, specifically with dental midline deviation, and high-arched palate were the most common findings. CONCLUSIONS: The present results contribute to knowledge on the orofacial manifestations of WBS. Since such patients with WBS may develop severe oral abnormalities, early detection and treatment can help improve their quality of life.

Nonsyndromic cleft lip and palate, gastric cancer and tooth agenesis.

BACKGROUND: To determine the frequency of nonsyndromic cleft lip and/or palate (NSCL/P) in first-degree relatives and to analyze the prevalence of tooth agenesis in patients with gastric cancer. MATERIAL AND METHODS: This cross-sectional, observational, case-control study included 798 patients attended at hospital Santa Casa in Montes Claros, Minas Gerais and Alfa Institute of Gastroenterology of the Federal University of the Minas Gerais. Information on basic demographic data and tooth agenesis of both groups and their family history of NSCL/P in first-degree relatives were evaluated. The collected information was stored in a database and analyzed using statistical program SPSS version 21.0 and the values with p<0.05 were considered statistically significant. RESULTS: Of the 798 patients, 113 (14.16%) consisted of the case group and 685 of the control group (85.84%). Non-Caucasian males were the most affected, although no differences among the groups were detected. Of all participants (n=798), 66 (8.27%) presented tooth agenesis and 25 (3.13%) presented oral cleft in first degree relative. CONCLUSIONS: Our results no found increase in the frequency of tooth agenesis in patients with gastric cancer and in the frequency of NSCL/P in the first-degree relatives of patients with gastric cancer.

Waardenburg syndrome type I: Dental phenotypes and genetic analysis of an extended family.

BACKGROUND: The aim of this study was to describe the pattern of inheritance and the clinical features in a large family with Waardenburg syndrome type I (WS1), detailing the dental abnormalities and screening for PAX3 mutations. MATERIAL AND METHODS: To characterize the pattern of inheritance and clinical features, 29 family members were evaluated by dermatologic, ophthalmologic, otorhinolaryngologic and orofacial examination. Molecular analysis of the PAX3 gene was performed. RESULTS: The pedigree of the family,including the last four generations, was constructed and revealed non-consanguineous marriages. Out of 29 descendants, 16 family members showed features of WS1, with 9 members showing two major criteria indicative of WS1. Five patients showed white forelock and iris hypopigmentation, and four showed dystopia canthorum and iris hypopigmentation. Two patients had hearing loss. Dental abnormalities were identified in three family members, including dental agenesis, conical teeth and taurodontism. Sequencing analysis failed to identify mutations in the PAX3 gene. CONCLUSIONS: These results confirm that WS1 was transmitted in this family in an autosomal dominant pattern with variable expressivity and high penetrance. The presence of dental manifestations, especially tooth agenesis and conical teeth which resulted in considerable aesthetic impact on affected individuals was a major clinical feature. CLINICAL RELEVANCE: This article reveals the presence of well-defined dental changes associated with WS1 and tries to establish a possible association between these two entities showing a new spectrum of WS1.

Cleidocranial dysplasia: oral features and genetic analysis of 11 patients.

BACKGROUND: Cleidocranial dysplasia (CCD) is a dominantly inherited autosomal disease characterized by typical bone defects including short stature, persistently open or delayed closure of the cranial sutures, and hypoplastic or aplastic clavicles. Oral features are frequent and include supernumerary teeth, delayed eruption or impaction of the permanent teeth, and malocclusion. Heterozygous mutations in RUNX2 gene, which encodes a transcription factor essential for osteoblast differentiation, were identified as the etiological cause of CCD. OBJECTIVE AND METHODS: Herein, we performed physical and radiographic examination and screening for RUNX2 mutations in 11 patients from five families with CCD. RESULTS: All patients demonstrated the classical phenotypes related to CCD. Families whose affected members had several dental alterations such as multiple impacted and supernumerary teeth demonstrated heterozygous missense mutations (R190Q and R225Q) that impair the runt domain of RUNX2. On the other hand, CCD patients from families with low frequency of dental abnormalities showed no mutation in RUNX2 or mutation outside of the runt domain (Q292fs→X299). CONCLUSION: The current findings suggest a correlation between dental alterations and mutations in the runt domain of RUNX2 in CCD patients. Further clinical and genetic studies are needed to clarify the relationship between phenotypes and genotypes in CCD and to identify other factors that might influence the clinical features of this uncommon disease.

Evaluation of MMP-1, MMP-10, TIMP-1, a-SMA and TGF-b1 in angiofibromas of tuberous sclerosis.

AIM: Tuberous sclerosis is a neurocutaneous syndrome characterized by affect multiple organs such as brain, kidneys, heart, eyes, lungs and skin. The aim of this study was to analyze the pattern of immunolocalization of markers MMP-1, MMP-10, TIMP-1, α-SMA and TGF-ß1 in oral and facial angiofibromas in individuals affected by tuberous sclerosis. METHODS: Microscopical analyses on hematoxilin-eosin and immunohistochemistry reactions were performed to analyze the previously cited biological markers pattern in orofacial angiofibromas. RESULTS: Reactivity was observed for MMP-1, MMP-10 and TGF-ß1, in addition to negative for TIMP-1 and α-SMA, except perivascular and epithelial staining for this. Concerning the intensity, a strong marking for MMP-1 in the basal layer of the epithelium, and a slight positivity in the suprabasal layers predominated. MMP-10 was slightly expressed in all epithelial layers. The connective tissue showed slight to moderate reactivity for MMP-1 and MMP-10. TIMP-1 demonstrated slight to moderate marking in the various layers of a single lesion and to TGF-ß1 expression showed varied in intensity staining both between lesions and between tissue layers. CONCLUSION: MMP-1, MMP-10 and TGF-ß1 exhibited reactivity in oral and cutaneous angiofibromas with heterogeneous distribution patterns among both tissue elements analyzed in the intensity of marking the same among the specimens. TIMP-1 showed reactivity predominantly negative in the specimens analyzed and α-SMA presented restricted to epithelial and perivascular regions of these lesions.

Chondrosarcoma involving the periodontum: clinicopathological and immunohistochemical features of a case study.

Chondrosarcoma is a rare flat bone neoplasm. Herein, we present the clinicopathological and immunohistochemical findings of a case affecting the periodontum. A 16-year-old girl presented a painless reddish mass in the lower anterior gingiva. Radiographs showed bone affected by vertical and horizontal loss and enlargement of periodontal space. The histopathological features showed atypical cartilage arranged in lobules compatible with chondrosarcoma. Immunohistochemistry showed that tumor cells were immunoreactive for the anti-vimentin and S-100 antibodies. Moreover, no tumor cells had been immunostained by anti-p53. Treatment consisted of chemotherapy, followed by radical surgery and postsurgery treatment with an association of radio and chemotherapy. After one year, no signs of recurrence have been observed.

Hereditary gingival fibromatosis: report of a five-generation family using cellular proliferation analysis.

BACKGROUND: Hereditary gingival fibromatosis (HGF) is an uncommon condition characterized by an accumulation of extracellular matrix resulting in a fibrotic enlargement of the gingiva. The goal of this article is to describe one kindred affected with HGF and discuss the diagnosis, treatment, and control of the disease. The pattern of inheritance, histopathologic characteristics, and proliferative potential of epithelial and mesenchymal cells of HGF are also emphasized. METHODS: To characterize the pattern of inheritance and the clinical appearance of gingival overgrowth, 117 family members were examined. The recurrence risk was estimated by the use of a genetic analysis program. Immunohistochemistry against the proliferating cell nuclear antigen (PCNA) and pKi-67 was performed to assess cellular proliferation of normal gingiva (NG) and HGF cells. RESULTS: Examination of the family pedigree demonstrated an autosomal dominant trait of inheritance, and a sibling recurrence risk of 0.085 and an offspring recurrence risk of 0.078, indicating that HGF was a consequence of genetic alteration with low penetrance. Unaffected and affected members transmitted the disease to their offspring. The affected patients showed a generalized but mild gingival overgrowth. Surgical treatment consisted of a combination of gingivectomy and gingivoplasty. Histologic examination showed that the gingival lesions of all patients were quite similar, with increased amounts of collagen fiber bundles in the connective tissue. Immunohistochemistry revealed that the proliferative potential of epithelial cells was significantly higher in the HGF group compared to the NG group, whereas mesenchymal cells from both groups were negative for the proliferative markers. CONCLUSION: Our data demonstrated that, in the studied family, HGF is transmitted by an autosomal dominant pattern with incomplete disease penetrance, and although the gingival enlargement resulted from an excessive accumulation of collagen fibers, HGF is characterized by an increase in the proliferation rate of epithelial cells.

Effect of transforming growth factor-beta1, interleukin-6, and interferon-gamma on the expression of type I collagen, heat shock protein 47, matrix metalloproteinase (MMP)-1 and MMP-2 by fibroblasts from normal gingiva and hereditary gingival fibromatosis.

BACKGROUND: Increased collagen and extracellular matrix deposition within the gingiva is the main characteristic feature of hereditary gingival fibromatosis (HGF). To date, it is not well established if these events are a consequence of alterations in the collagen and other extracellular matrix molecules synthesis or disturbances in the homeostatic equilibrium between synthesis and degradation of extracellular matrix molecules. Cytokines are important regulators of expression of the profibrogenic genes, including type I collagen and its molecular chaperone heat shock protein (Hsp)47 and proteolytic enzymes degrading extracellular matrix such as matrix metalloproteinases-1 and -2 (MMP-1 and MMP-2). METHODS: In this study, we analyzed the expression and production of type I collagen, Hsp47, MMP-1, and MMP-2 in normal gingiva (NG) and HGF fibroblasts, and investigated the effects of transforming growth factor-beta1 (TGF-beta1), interleukin-6 (IL-6) and interferon-gamma (IFN-gamma) on the expression of these genes by NG and HGF fibroblasts. RESULTS: Our results obtained from semi-quantitative reverse transcription-polymerase chain reactions (RT-PCR), Western blots, enzyme-linked immunosorbent assays (ELISA), and enzymographies clearly demonstrated that the expression and production of type I collagen and Hsp47 were significantly higher in fibroblasts from HGF than from NG, whereas MMP-1 and MMP-2 expression and production were lower in fibroblasts from HGF patients. Addition of TGF-beta1 and IL-6, which are produced in greater amounts by HGF fibroblasts, promoted an increase in type I collagen and Hsp47 and a decrease in MMP-1 and MMP-2 expression. IFN-gamma reduced both type I collagen and Hsp47 expression, whereas it had a slight effect on the expression of MMP-1 and MMP-2. CONCLUSION: These patterns of expression and production suggest that enhanced TGF-beta1 and IL-6 production simultaneously increase the synthesis and reduce the proteolytic activities of fibroblasts from patients with HGF, which may favor the accumulation of extracellular matrix observed in patients with this condition.

Cyclosporin A induces proliferation in human gingival fibroblasts via induction of transforming growth factor-beta1.

BACKGROUND: Cyclosporin A (CsA) is a widely used immunosuppressant that causes significant side effects including gingival overgrowth. The pathogenesis of this condition is not fully understood; however, recent studies show that CsA regulates the transcription of several cytokines including transforming growth factor-beta 1 (TGF-beta1). In this study, we evaluated the effects of CsA and TGF-beta1 on human normal gingival (NG) fibroblast proliferation, and explored a possible autocrine stimulation of TGF-beta1 as a cellular regulator of proliferation induced by CsA in NG fibroblasts. METHODS: NG fibroblast cell lines were incubated with increasing concentrations of CsA or TGF-beta1 and the proliferation index determined by automatic cell counting, BrdU incorporation, PCNA expression, and mitotic potential. To determine the effect of TGF-beta1 on the proliferation rate of NG fibroblasts under CsA treatment, NG fibroblast cultures were simultaneously treated with CsA and antisense oligonucleotides against the translation-start site of the TGF-beta1 mRNA. RESULTS: Treatment of NG fibroblasts with CsA or TGF-beta1 significantly stimulated the cell proliferation in a dose-dependent manner. Furthermore, neutralization of TGF-beta1 production in CsA-treated NG fibroblasts inhibited CsA's effect on NG fibroblast proliferation, demonstrating an autocrine stimulatory effect of TGF-beta1 in CsA-treated NG fibroblast proliferation. CONCLUSION: The results presented here suggest that CsA stimulatory induction of NG fibroblast proliferation is mediated via TGF-beta1 in an autocrine fashion.

Expression of matrix metalloproteinases in cyclosporin-treated gingival fibroblasts is regulated by transforming growth factor (TGF)-beta1 autocrine stimulation.

BACKGROUND: Gingival overgrowth is a common side effect following the administration of cyclosporin A (CsA). The pathogenesis of this condition is not fully understood; however, recent studies show that CsA regulates the transcription of several cytokines including transforming growth factor-beta1 (TGF-beta1). The aim of this study was to investigate the potential role of TGF-beta1 in the pathogenesis of CsA-induced gingival overgrowth, exploring a possible autocrine stimulation of TGF-beta1 as a cellular regulator of synthesis of matrix metalloproteinases (MMPs) and its tissue inhibitors (TIMPs). METHODS: Gingival fibroblasts from human normal gingiva were incubated with increasing concentrations of CsA, cultured for 24 hours, and the expression and production of TGF-beta1 determined by semiquantitative reverse transcriptase-polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA), respectively. MMP and TIMP mRNA expression levels were also analyzed by RT-PCR. To determine the effect of TGF-beta1 on the expression of MMP and TIMP by human gingival fibroblasts under CsA treatment, human gingival fibroblast cultures were treated with sense oligonucleotides (SON) or antisense oligonucleotides (AON). RESULTS: CsA simultaneously stimulated TGF-beta1 expression and production and inhibited expression of MMP-1 and MMP-2 by human gingival fibroblasts, whereas CsA has a slight effect on TIMP-1 and TIMP-2 expression. AON reduced TGF-beta1 production as demonstrated by ELISA, whereas TGF-beta1 mRNA expression levels were not significantly modified. The inhibition of TGF-beta1 production by AON modulated MMP expression, demonstrating the autocrine inhibitory effect of TGF-beta1 in CsA-treated human gingival fibroblasts. CONCLUSIONS: The data presented here suggest that TGF-beta1 in an autocrine fashion may contribute to a reduction of proteolytic activity of human gingival fibroblasts in CsA-induced gingival overgrowth, which favors the accumulation of extracellular matrix.

Imaging evalution of the gingival fibromatosis and dental abnormalities syndrome.

OBJECTIVE: The purpose of this study was to evaluate the dentomaxillofacial imaging features of one family affected by the gingival fibromatosis (GF) and dental abnormalities (DA) syndrome. METHODS: Conventional radiographs (periapical and panoramic) and cone beam CT (CBCT) were performed in nine members of this family: four were affected by the syndrome and five were not. RESULTS: The four affected members demonstrated mild generalized GF in association with DA, including hypoplastic amelogenesis imperfecta, intrapulpal calcifications, delay on tooth eruption and pericoronal radiolucencies in unerupted teeth. None of these oral changes were identified in the five unaffected members. All nine members presented alterations in the paranasal sinuses and mucosal thickening of the maxillary sinus was the most common finding. CONCLUSION: Family members not affected by the syndrome showed similar alterations in the paranasal sinuses and CBCT was useful to characterize the dentomaxillofacial features of this new syndrome associating GF and DA.

Peripheral odontogenic fibroma (WHO type) of the newborn: a case report.

AIM: The present paper reports a case of peripheral odontogenic fibroma (POF) (WHO type) in a newborn. The differential diagnosis and treatment were discussed. BACKGROUND: POF is well described in the literature, but this is the first report in a newborn. PATIENT: A 4-month-old female newborn was referred to our department because of an exophytic, sessile, firm, and well-delimited lesion on the right upper alveolar ridge. The covering mucosa was apparently normal. The lesion measuring 10 x 3 mm was present since birth. The clinical diagnosis of congenital granular cell tumour (congenital epulis) or dental lamina cyst of the newborn was made. A conservative excisional biopsy was performed under local anaesthesia, and the specimen was submitted to histopathological examination. RESULTS: The microscopic examination revealed a pattern of POF (WHO type). Normal primary incisors teeth eruption, and no signs of recurrence were noted on 16 months follow-up. CONCLUSION: Despite the rarity of POF in a newborn, this lesion should be included as a possible diagnosis to focal gingival growth.

Testosterone stimulates proliferation and inhibits interleukin-6 production of normal and hereditary gingival fibromatosis fibroblasts.

Hereditary gingival fibromatosis (HGF) is a rare oral condition characterized by a slow and progressive enlargement of the gingiva, involving both the maxilla and mandible. In vitro, HGF fibroblasts demonstrate a proliferative index significantly higher than fibroblasts from normal gingiva (NG). The objective of this study was to determine the effect of dihydrotestosterone on the proliferation of gingival fibroblasts derived from patients with HGF (n = 4) and from four healthy individuals. Additionally, we analyzed the effect of dihydrotestosterone on interleukin-6 (IL-6) production and determined the expression levels of androgen receptors in NG and HGF fibroblasts. Gingival fibroblasts from NG and HGF were incubated with increasing concentrations of dihydrotestosterone with or without androgen blockers, and cultured for 24 h, and the proliferation index was determined by automated cell counter. IL-6 production, in this system, was quantified using a "capture" enzyme-linked immunosorbent assay (ELISA). Semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) was performed to measure the mRNA expression of androgen receptors. The results indicated that dihydrotestosterone simultaneously downregulates the production of IL-6 and upregulates the cell proliferation. Finasteride and cyprosterone acetate, two anti-androgens, partially reversed these effects. Androgen receptor mRNA expression was identified in both NG and HGF fibroblasts; however, the levels in NG were higher than those observed in HGF. These results show that testosterone coordinates the proliferation and production of IL-6 of normal and HGF fibroblasts.

Cyclosporin A inhibits production and activity of matrix metalloproteinases by gingival fibroblasts.

Cyclosporin A (CyA) is a potent immunosuppressor used in organ transplantation and in the management of various autoimmune diseases. Gingival overgrowth is one of the side-effects of the CyA-treatment, affecting the attached gingiva of 25-81% of treated patients. To investigate the production and activity of matrix metalloproteinases (MMPs) in the CyA-induced gingival overgrowth, 2 well-documented models were utilized: the in vivo CyA-induced rat gingival overgrowth and primary cultures of human gingival fibroblasts treated with CyA. Our results obtained from the Western blot assays demonstrated clearly that the production of MMP-1 and MMP-3 was significantly inhibited by CyA at similar concentrations found in the serum of patients undergoing CyA-treatment. Moreover, the gelatinolytic activity of MMP-2 was also reduced both in cultured fibroblasts and in the rat CyA-induced gingival overgrowth. Taken together, the data presented here suggest that these inhibitory effects may contribute to the extracellular matrix (ECM) components accumulation in the CyA-induced gingival overgrowth.

Expression of Matrix Metalloproteinases in Cyclosporin-Treated Gingival Fibroblasts Is Regulated by Transforming Growth Factor (TGF)-ß1 Autocrine Stimulation / x

Background: Gingival overgrowth is a common side effect following the administration of cyclosporin A (CsA). The pathogenesis of this condition is not fully understood; however, recent studies show that CsA regulates the transcription of several cytokines including transforming growth factor-ß1 (TGF-ß1). The aim of this study was to investigate the potential role of TGF-ß1 in the pathogenesis of CsA-induced gingival overgrowth, exploring a possible autocrine stimulation of TGF-ß1 as a cellular regulator of synthesis of matrix metalloproteinases (MMPs) and its tissue inhibitors (TIMPs). Methods: Gingival fibroblasts from human normal gingiva were incubated with increasing concentrations of CsA, cultured for 24 hours, and the expression and production of TGF-ß1 determined by semiquantitative reverse transcriptase-polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA), respectively. MMP and TIMP mRNA expression levels were also analyzed by RT-PCR. To determine the effect of TGF-ß1 on the expression of MMP and TIMP by human gingival fibroblasts under CsA treatment, human gingival fibroblast cultures were treated with sense oligonucleotides (SON) or anti-sense oligonucleotides (AON). Results: CsA simultaneously stimulated TGF-ß1 expression and production and inhibited expression of MMP-1 and MMP-2 by human gingival fibroblasts, whereas CsA has a slight effect on TIMP-1 and TIMP-2 expression. AON reduced TGF-ß1 production as demonstrated by ELISA, whereas TGF-ß1 mRNA expression levels were not significantly modified. The inhibition of TGF-ß1 production by AON modulated MMP expression, demonstrating the autocrine inhibitory effect of TGF-ß1 in CsA-treated human gingival fibroblasts. Conclusions: The data presented here suggest that TGF-ß1 in an autocrine fashion may contribute to a reduction of proteolytic activity of human gingival fibroblasts in CsA-induced gingival overgrowth, which favors the accumulation of extra-cellular matrix