Proteoglycans of human gingival epithelium and connective tissue.
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ABSTRACT:
SUBMITTER: Bartold PM
PROVIDER: S-EPMC1154335 | biostudies-other | 1983 Apr
REPOSITORIES: biostudies-other
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Project description:Proteoglycans extracted from human gingival epithelium appear to contain a proportion of molecules that will interact with hyaluronic acid to form macromolecular aggregates. In contrast, proteoglycans from underlying connective tissue behaved differently. The interactions of hyaluronic acid with proteoglycans from either epithelium or cartilage may be similar, but not necessarily identical.
| S-EPMC1161579 | biostudies-other
Project description:Connective tissue growth factor (CCN2/CTGF) mediates transforming growth factor-β (TGF-β)-induced fibrosis. Drug-induced gingival overgrowth is tissue specific. Here the role of the phosphoinositol 3-kinase (PI3K) pathway in mediating TGF-β1-stimulated CCN2/CTGF expression in primary human adult gingival fibroblasts and human adult lung fibroblasts was compared. Data indicate that PI3K inhibitors attenuate upregulation of TGF-β1-induced CCN2/CTGF expression in human gingival fibroblasts independent of reducing JNK MAP kinase activation. Pharmacologic inhibitors and small interfering (si)RNA-mediated knockdown studies indicate that calcium-dependent isoforms and an atypical isoform of protein kinase C (PKC-δ) do not mediate TGF-β1-stimulated CCN2/CTGF expression in gingival fibroblasts. As glycogen synthase kinase-3β (GSK-3β) can undergo phosphorylation by the PI3K/pathway, the effects of GSK-3β inhibitor kenpaullone and siRNA knockdown were investigated. Data in gingival fibroblasts indicate that kenpaullone attenuates TGF-β1-mediated CCN2/CTGF expression. Activation of the Wnt canonical pathways with Wnt3a, which inhibits GSK-3β, similarly inhibits TGF-β1-stimulated CCN2/CTGF expression. In contrast, inhibition of GSK-3β by Wnt3a does not inhibit, but modestly stimulates, CCN2/CTGF levels in primary human adult lung fibroblasts and is β-catenin dependent, consistent with previous studies performed in other cell models. These data identify a novel pathway in gingival fibroblasts in which inhibition of GSK-3β attenuates CCN2/CTGF expression. In adult lung fibroblasts inhibition of GSK-3β modestly stimulates TGF-β1-regulated CCN2/CTGF expression. These studies have potential clinical relevance to the tissue specificity of drug-induced gingival overgrowth.
| S-EPMC3761177 | biostudies-literature
Project description:OBJECTIVES:The aim of this study was to compare outcomes of the modified coronally advanced tunnel technique (MCAT) combined with subepithelial connective tissue graft (SCTG) with or without enamel matrix derivative (EMD), in the treatment of gingival recession types 1 and 2. MATERIALS AND METHODS:A total of 20 patients with 150 multiple gingival recessions (GR) were included in the study. On one side, MCAT was combined with SCTG and EMD (tests), whereas MCAT with SCTG was applied on the contralateral side (controls). Clinical parameters were measured at baseline and 6 months after surgery. Visual analog scales (VAS) and questionnaires were used to assess patient-reported outcomes and the root coverage esthetic score (RES) for professional esthetic evaluation. RESULTS:MCAT+SCTG+EMD was not superior with regard to root coverage. At 6 months, average root coverage (ARC) was 87.4% for SCTG+EMD-treated and 90.9% for SCTG-treated defects (p?=?0.4170). Complete root coverage (CRC) was observed in 86.7% (tests) and 85.3% (controls) of the cases (p?=?0.9872). Significantly less pain was reported using VAS (p?=?0.0342) post-operatively in the SCTG+EMD group. Professional assessment of esthetic outcomes using RES showed a significant difference (9.25 versus 8.71, p?=?0.0103) in favor of the test group. CONCLUSIONS:Both treatment modalities were equally effective in treatment of multiple GR and led to similar improvements in clinical parameters. However, the application of EMD as an adjunct resulted in less post-operative pain and better professionally assessed esthetic outcomes. CLINICAL RELEVANCE:Patients' early morbidity and 6-month esthetic outcomes following GR coverage with MCAT might be influenced by means of EMD utilization.
| S-EPMC7666664 | biostudies-literature
Project description:Hereditary gingival fibromatosis [HGF, (MIM 135300)], a rare benign oral condition, has several adverse consequences such as aesthetic changes, malocclusion, speech impediments, and abnormal dentition. However, relatively few studies have addressed the beneficial effects of thick gingival tissues in resisting external stimuli. In this report, we present a unique case of a family affected by HGF that manifests as a ‘healthy’ gingiva. Human β-defensins (hBDs) are known to play a pivotal role in the clearance and killing of various microbes, and contribute to maintaining a healthy oral environment, which is currently emerging research area. However, the expression pattern and localisation of hBDs in patients with HGF have not yet been reported. hBD-2 and hBD-3 in the pedigree we collected had relatively elevated expression. High hBD levels in the gingival tissue of patients from the family may be beneficial in protecting oral tissue from external stimuli and promoting periodontal regeneration, but their role and the mechanisms underlying HGF need to be clarified.
| S-EPMC8594454 | biostudies-literature
Project description:Proliferative vitreoretinopathy (PVR) is a disease leading to the formation of contractile preretinal membranes (PRMs) and is one of the leading causes of blindness. Connective tissue growth factor (CTGF) has been identified as a possible key determinant of progressive tissue fibrosis and excessive scarring. Therefore, the present study investigated the role and mechanism of action of CTGF in PVR. Immunohistochemical staining was performed to detect the expression of CTGF, fibronectin and collagen type III in PRMs from patients with PVR. The effects and mechanisms of recombinant human CTGF and its upstream regulator, TGF‑β1, on epithelial‑mesenchymal transition (EMT) and the synthesis of extracellular matrix (ECM) by retinal pigment epithelium (RPE) cells were investigated using reverse transcription‑quantitative PCR, western blotting and a [3H]proline incorporation assay. The data indicated that CTGF, fibronectin and collagen type III were highly expressed in PRMs. In vitro, CTGF significantly decreased the expression of the epithelial markers ZO‑1 and E‑cadherin and increased that of the mesenchymal markers fibronectin, N‑cadherin and α‑smooth muscle actin in a concentration‑dependent manner. Furthermore, the expression of the ECM protein collagen type III was upregulated by CTGF. However, the trends in expression for the above‑mentioned markers were reversed after knocking down CTGF. The incorporation of [3H]proline into RPE cells was also increased by CTGF. In addition, 8‑Bromoadenosine cAMP inhibited CTGF‑stimulated collagen synthesis and transient transfection of RPE cells with a CTGF antisense oligonucleotide inhibited TGF‑β1‑induced collagen synthesis. The phosphorylation of PI3K and AKT in RPE cells was promoted by CTGF and TGF‑β1 and the latter promoted the expression of CTGF. The results of the present study indicated that CTGF may promote EMT and ECM synthesis in PVR via the PI3K/AKT signaling pathway and suggested that targeting CTGF signaling may have a therapeutic or preventative effect on PVR.
| S-EPMC8008218 | biostudies-literature
Project description:ObjectivesTo investigate factors that influence 12-month outcomes after treatment of multiple gingival recessions (GR) with modified coronally advanced tunnel (MCAT) and subepithelial connective tissue graft (SCTG) with enamel matrix derivative (EMD) (tests) or without (controls).Materials and methodsTwenty patients with 150 GR were treated. Logistic regression models were used to identify baseline parameters that could predict 12-month average root coverage (ARC), complete root coverage (CRC), root esthetic coverage score (RES), gain in keratinized tissue width (KTW), and gain in gingival thickness (GT).ResultsThe likelihood of ARC > 85% increased sevenfold (odds ratio [OR] = 7.33; 95% confidence interval [CI] = 2.43-12.12), of achieving CRC: 21-fold (OR = 21.23; 95% CI = 10.21-45.32), and of gaining RES = 10: tenfold (OR = 10.23; 95% CI = 5.78-32.23) in favor of EMD-treated sites. With each 1-mm2 increase in baseline avascular exposed root surface area (AERSA), the odds of failure (ARC ≤ 85%, not achieving CRC and postoperative GT ≤ 2 mm) increased almost fourfold (OR = 3.56; 95% CI = 1.98-10.19), fourfold (OR = 4.23; 95% CI = 1.11-9.02), and nearly sixfold (OR = 5.76; 95% CI = 2.43-12.87), respectively. The greater the baseline GT, the more likely the chance of achieving CRC (OR = 10.23; 95% CI = 8.37-16.23) and RES = 10 (OR = 5.50; 95% CI = 3.34-16.43). All models exhibited fair to excellent discrimination and satisfactory calibration.ConclusionsBased on logistic regression, EMD application improved postoperative ARC, CRC and RES; baseline AERSA predicted 12-month ARC, CRC, and GT gain, whereas baseline GT was a predictor of achieving CRC and perfect RES.Clinical relevanceAdditional use of EMD, lower baseline AERSA, and greater baseline GT significantly increase the odds of obtaining better outcomes 12 months after MCAT + SCTG technique.
| S-EPMC8791902 | biostudies-literature
Project description:Human beta-defensin-1 (hBD-1) is a member of the family of small cationic antimicrobial peptides that have been identified in several mucosal epithelia. Because human gingival epithelium is a site that is constantly challenged by oral microorganisms, we examined the expression of hBD-1 in human gingival epithelial and fibroblast cell cultures and tissue samples. Cell cultures were challenged with cell wall extracts of Porphyromonas gingivalis or Fusobacterium nucleatum, Escherichia coli lipopolysaccharide, tumor necrosis factor alpha, or phorbol myristate acetate. hBD-1 mRNA was detected in unstimulated and stimulated cultures by reverse transcription (RT)-PCR using several primer sets specific for hBD-1. Gingival epithelial cells, but not gingival fibroblasts, expressed a product of the predicted size for hBD-1 mRNA. The sequence of the PCR product was identical to that of hBD-1. hBD-1 mRNA expression was not significantly modulated by any of the stimulants tested. Human gingival tissues from noninflamed and inflamed sites were also analyzed by RT-PCR. hBD-1 mRNA was expressed in all tissue samples. The relative expression of hBD-1 mRNA was similar in noninflamed and inflamed tissues obtained from each of four patients undergoing treatment for periodontitis. However, the relative expression of hBD-1 mRNA varied in gingival biopsies obtained from 15 different normal individuals, and the relative hBD-1 expression was unrelated to interleukin-8 expression. Our findings show the constitutive expression of hBD-1 mRNA in cultured epithelial cells and gingival tissues but not gingival fibroblasts. These findings suggest that expression of hBD-1 may play a role as part of the innate host defenses in maintaining normal gingival health.
| S-EPMC108509 | biostudies-literature
Project description:BACKGROUND:Connective tissue growth factor (CCN2; CTGF) is a newly identified growth factor, which is involved in the regulation of wound repair and fibrosis. Because there is variation among individuals with respect to tissue response to injury, genetic factors might be involved in the final outcome of tissue repair or scarring. For example, polymorphisms in the promoter region of genes, such as those encoding transforming growth factor beta1 (TGF-beta1), interleukin 10 (IL-10), and tumour necrosis factor alpha (TNF-alpha), influence transcriptional responses and are thought to contribute to the dysregulation of these genes in pathological conditions. AIM:To investigate whether the promoter region of the ccn2 (ctgf) gene contains polymorphic sequences that might account for differential expression. MATERIALS/METHODS:Seventy seven human DNA samples were sequenced-45 were from healthy controls and 32 were from patients with ischaemic heart disease (IHD)-using M13 tailed sequence specific ccn2 (ctgf) primers for amplification of a 600 bp fragment upstream of the transcription start site. Amplicons were bidirectionally sequenced with a dye primer M13 forward and reverse sequencing kit. RESULTS:A C to G substitution was identified at position -132 in one of the patients with IHD. Moreover, in five of the 32 patients with IHD and in six of the 45 healthy controls, a G to C polymorphism was found at position -447. These substitutions at -132 and -447 are thought to lie within predicted binding domains for the transcription factors Pbx-1 and MZF1, respectively. In addition, insertions at position -43 (G), -47 (C), -71 (G) and a C to T substitution at position -198 were found in all DNA samples compared with the published ccn2 (ctgf) promoter sequence. These corrections do not involve sequences predicted to function as transcription factor binding sites. CONCLUSION:Sequence analysis of the ccn2 (ctgf) promoter of 77 human DNA samples has revealed corrections and polymorphic sites. The latter lie within putative regulatory elements.
| S-EPMC1187061 | biostudies-literature
Project description:PurposeThe aim of this study was to compare the efficacy of the tunnel technique for root coverage using a new xenogeneic acellular dermal matrix vs. connective tissue grafting (CTG) for the treatment of multiple maxillary adjacent recessions (recession type 1) at 12 months postoperatively.MethodsThis study enrolled 12 patients with at least 3 contiguous, bilateral, symmetrical maxillary gingival recessions (i.e., at least 6 recessions per patient). In total, 74 recessions were treated using the modified coronally advanced tunnel (MCAT) technique combined with a novel porcine-derived acellular dermal matrix (PADM) at 37 test sites or CTG at 37 control sites. The following clinical parameters were measured: recession height, clinical attachment level, width of keratinized tissue, probing depth, recession width, gingival thickness, mean root coverage (MRC), and complete root coverage (CRC). Comparisons between test and control groups were made for pain visual analog scale scores at 14 days.ResultsAt 12 months, the MCAT with PADM (test) yielded a statistically significant improvement in all clinical parameters studied. MRC was significantly higher on the control sides (80.6%±23.7%) than on the test sides (68.8%±23.4%). Similarly, CRC was 48.7%±6.8% on the control sides (CTG), in contrast to 24.3%±8.2% on the test sides (PADM). Statistically significant differences were observed in favor of the control sides for all clinical parameters studied. Nevertheless, the MCAT in adjunction with PADM was clearly superior at reducing mean and maximum patient-reported postoperative pain intensity and pain duration in the first week after surgery.ConclusionsThe use of PADM to treat multiple recessions improved clinical parameters at 12 months, but these outcomes were nevertheless poorer than those observed for CTG. However, PADM reduced morbidity, particularly the pain experienced by patients.Trial registrationClinicalTrials.gov Identifier: NCT03162016.
| S-EPMC8090794 | biostudies-literature
Project description:Scar formation is the typical endpoint of wound healing in adult mammalian tissues. An overactive or prolonged fibrogenic response following injury leads to excessive deposition of fibrotic proteins that promote tissue contraction and scar formation. Although well-defined in the dermal tissue, the progression of fibrosis is less explored in other connective tissues, such as the vocal fold. To establish a physiologically relevant 3D model of loose connective tissue fibrosis, we have developed a synthetic extracellular matrix using hyaluronic acid (HA) and peptidic building blocks carrying complementary functional groups. The resultant network was cell adhesive and protease degradable, exhibiting viscoelastic properties similar to the human vocal fold. Human mesenchymal stem cells (hMSCs) were encapsulated in the HA matrix as single cells or multicellular aggregates and cultured in pro-fibrotic media containing connective tissue growth factor (CTGF) for up to 21 days. hMSCs treated with CTGF-supplemented media exhibited an increased expression of fibrogenic markers and ECM proteins associated with scarring. Incorporation of α-smooth muscle actin into F-actin stress fibers was also observed. Furthermore, CTGF treatment increased the migratory capacity of hMSCs as compared to the CTGF-free control groups, indicative of the development of a myofibroblast phenotype. Addition of an inhibitor of the mitogen-activated protein kinase (MAPK) pathway attenuated cellular expression of fibrotic markers and related ECM proteins. Overall, this study demonstrates that CTGF promotes the development of a fibrogenic phenotype in hMSCs encapsulated within an HA matrix and that the MAPK pathway is a potential target for future therapeutic endeavors towards limiting scar formation in loose connective tissues.
| S-EPMC7654958 | biostudies-literature