Oral pathology and oral medicine in Latin American countries: current stage.

BACKGROUND: Oral Pathology (OP) and Oral Medicine (OM) are specialties in dentistry whose main objective is the diagnosis and treatment of oral and maxillofacial diseases, and aspects related to the academic training of professionals and fields of practice are distinct and heterogeneous around the world. This study aimed to evaluate professional training and areas of activity in OP and OM in Latin American countries. MATERIAL AND METHODS: A questionnaire was sent to 11 countries, with a professional in each country responsible for answering it. The questionnaire had 21 questions related to the process of professional training, areas of practice, the existence of scientific events in each country, and also collected demographic and population information. RESULTS: OP and OM are practiced in all the countries studied, but the specialty is not recognized in all of them. Brazil was the first to recognize both as a specialty. Postgraduate programs designed to train specialists are available in various countries. Two countries offer residency programs, 6 countries provide specialization courses, 6 offer master's programs, and 3 have doctoral programs. Brazil boasts the highest number of undergraduate courses (n=412), while Uruguay has the lowest (n=2). Professional societies representing the specialty exist in ten countries. Brazil has the highest number of OP and OM specialists (n=422 and 1,072), while Paraguay has the smallest number (n=1 and 3). CONCLUSIONS: Although both specialties are widely practiced around the globe, professional training, the number of dentists trained and the fields of professional practice are very different between the countries studied.

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.

2p24.2 (rs7552) is a susceptibility locus for nonsyndromic cleft lip with or without cleft palate in the Brazilian population.

The population of Brazil is highly admixed, with each individual showing variable levels of Amerindian, European and African ancestry, which may interfere in the genetic susceptibility of known risk loci to nonsyndromic cleft lip with or without cleft palate (NSCL±P). Here, we investigated 5 reported genome-wide loci for NSCL±P in an ancestry-structured case-control study containing 1697 Brazilian participants (831 NSCL±P and 866 healthy controls). SNPs rs7552 in 2q24.2, rs8049367 in 16p13.3, rs1880646, rs7406226, rs9891446 in 17p13, rs1588366 in 17q23.2 and rs73039426 in 19q13.11 were genotyped using TaqMan allelic discrimination assays and genomic ancestry was estimated using a panel of 40 biallelic short insertion/deletion polymorphic markers informative of the Brazilian population. Logistic regression analysis of the single-markers revealed rs7552 in 2p24.2 as a susceptibility risk marker for NSCL±P, yielding an odds ratio (OR) of 1.71 (95% confidence interval (CI): 1.31-2.24, P = 9 × 10-6 ) in the homozygous state. Several SNP-SNP interactions containing rs7552 reached significance after adjustment for multiple tests (both Bonferroni assumption and 1000 permutation test), with the most significant interaction involving the 3-loci among rs7552, rs9891446 and rs73039426 (P = 6.1 × 10-9 and p1000 permutation = 0.001). Our study is the first to support the association of rs7552 in 2p24.2 with NSCL±P in the highly admixed Brazilian population.

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.

Comparison of digit ratio (2D:4D) between Brazilian men with and without prostate cancer.

BACKGROUND: Digit ratio (2D:4D) has been suggested as a proxy biomarker for prenatal androgen activity and has been linked to prostate cancer, as the genes that regulate the formation and differentiation of the fingers are also related to the carcinogenesis of prostate cancer. To investigate the possible correlation between right hand, left hand and right hand minus left hand (DR-L) 2D:4D and prostate cancer of Brazilian subjects by comparing 2D:4D ratios of individuals diagnosed with prostate cancer and individuals without the disease. Also, to inquire the relationship between 2D:4D and severity of prostate cancer through Gleason scores. METHODS: Digital measurements of the lengths of the index and ring fingers of both hands of patients diagnosed with prostate cancer (PCA group, n=100) and healthy control individuals (n=100) were obtained using a digital vernier caliper. Means of the 2D:4D ratios were compared. Data were analyzed by the Student's t-test for unpaired samples, Mann-Whitney test and Spearman's correlation with a significance level of 5%. RESULTS: The PCA group presented significantly lower right and left 2D:4D (P=0.001 and P=0.002, respectively) in comparison to healthy controls, but DR-L were not significantly different between groups (P=0.589). In addition, digit ratios were not correlated to Gleason score for either hand or in DR-L. CONCLUSIONS: 2D:4D seems to be a marker for screening patients for prostate cancer in an admixed population, as males with prostate cancer present lower 2D:4D than healthy subjects. On the other hand, 2D:4D does not appear to be associated with the severity of prostate cancer.

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.

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.

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.

Lack of association between IRF6 polymorphisms (rs2235371 and rs642961) and non-syndromic cleft lip and/or palate in a Brazilian population.

BACKGROUND: Interferon regulatory factor 6 (IRF6) gene has emerged as a potential susceptibility gene for non-syndromic cleft lip and/or palate (NSCL/P) in different populations. The aim of this study was to determine the association of IRF6 rs2235371 and rs642961 polymorphisms with NSCL/P in a Brazilian population. METHODS: Two hundred and twenty-eight patients affected by NSCL/P and 126 healthy individuals were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. RESULTS: Overall genotype distributions of rs2235371 and rs642961 polymorphisms were as expected by Hardy-Weinberg equilibrium test. The rs2235371 polymorphic genotype GA was identified in 10.1% of the patients with NSCL/P and in 10.3% of the control group, revealing no statistical difference. Similarly, the frequency of rs642961 minor genotypes (GA and AA) was quite similar between control group (28.6%) and NSCL/P group (25.4%), without significant difference. CONCLUSION: Our findings are consistent with a lack of involvement of IRF6 rs2235371 and rs642961 polymorphisms in the NSCL/P pathogenesis in the Brazilian population.

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.

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.

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 Sec61 alpha in F9 and P19 teratocarcinoma cells after retinoic acid treatment.

Nascent procollagen peptides and other secretory proteins are transported across the endoplasmic reticulum (RE) membrane through a protein-conducting channel called the translocon. Sec61 alpha, a multispanning membrane translocon protein, has been implicated as essential for translocation of polypeptides chains into the cisterns of the ER. However, it is not known whether Sec61 alpha is ubiquitously expressed in collagen producing teratocarcinoma cells. Furthermore, the production, expression, and utilization of Sec61 alpha may depend on the cell differentiation stage. Stem cells from many cultured teratocarcinoma cell lines such as F9 and P19 cells are capable of differentiation in response to low retinoic acid concentrations. This differentiation of the tumorigenic stem cells results in tumorigenicity loss. For this study, mouse F9 and P19 teratocarcinoma cells were grown in culture medium treated with or without retinoic acid. Expression of Sec61 alpha was determined by reverse trancriptase polimerase chain reaction (RT-PCR). In untreated conditions, F9 cells expressed undetected Sec61 alpha amounts. It was also demonstrated that Sec61 alpha expression is stimulated in F9 cells after retinoic acid treatment for 72 hours. No changes were found in Sec61 alpha expression in P19 cells after retinoic acid treatment. These data indicate that the expression of Sec61 alpha is enhanced with retinoic acid induced differentiation of F9 teratocarcinoma cells.

Expression of Sec61alpha in F9 and P19 teratocarcinoma cells after retinoic acid treatment

Nascent procollagen peptides and other secretory proteins are transported across the endoplasmic reticulum (RE) membrane through a protein-conducting channel called the translocon. Sec61alpha, a multispanning membrane translocon protein, has been implicated as essential for translocation of polypeptides chains into the cisterns of the ER. However, it is not known whether Sec61alpha is ubiquitously expressed in collagen producing teratocarcinoma cells. Furthermore, the production, expression, and utilization of Sec61alpha may depend on the cell differentiation stage. Stem cells from many cultured teratocarcinoma cell lines such as F9 and P19 cells are capable of differentiation in response to low retinoic acid concentrations. This differentiation of the tumorigenic stem cells results in tumorigenicity loss. For this study, mouse F9 and P19 teratocarcinoma cells were grown in culture medium treated with or without retinoic acid. Expression of Sec61alpha was determined by reverse trancriptase polimerase chain reaction (RT-PCR). In untreated conditions, F9 cells expressed undetected Sec61alpha amounts. It was also demonstrated that Sec61alpha expression is stimulated in F9 cells after retinoic acid treatment for 72 hours. No changes were found in Sec61alpha expression in P19 cells after retinoic acid treatment. These data indicate that the expression of Sec61alpha is enhanced with retinoic acid induced differentiation of F9 teratocarcinoma 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.