Expression of Epithelial-Mesenchymal Transition (EMT) Associated Markers in Peri-implant Tissues From Peri-implantitis Patients: A Case-Control Study
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 40
- 试验地点
- 1
- 主要终点
- Peri-implant probing pocket depth (PPD)
研究概览
简要总结
Peri-implantitis is an inflammation of bacterial etiology characterized by inflammation of mucous membranes and bone loss around the dental implant. A specific dental plaque bacteria could stimulate host cells, including the junctional epithelium, to secrete a range of pro-inflammatory cytokines involved in initiating the epithelial-mesenchymal transition (EMT) process. EMT has been described as the transdifferentiation of epithelial cells into motile mesenchymal cells.
Moreover, cytokines and bacterial products have been highlighted as EMT-predisposing factors. The EMT process could render epithelial cells to lose their cell-cell adhesion and cell polarity that lend these cells to lose their function as an integrated epithelial barrier.
E-cadherin is a calcium-dependent cell adhesion molecule that establishes cell-cell adhesion that plays a critical role in maintaining a barrier function in the human epithelium, including gingiva. The loss of E-cadherin is one of the most common biological indicators for EMT. In contrast, vimentin is an intermediate filament expressed in mesenchymal cells and is a canonical marker for EMT, which also promotes cell motility and an invasive phenotype.
It is largely reported that EMT is regulated by various transcriptional factors such as Snail Family Transcriptional Repressor SNAIL1 and SNAIL2, zinc-finger E-box-binding (ZEB)1 and ZEB2 and TWIST transcription factors that suppress epithelial marker genes, and activate genes related with the mesenchymal phenotype.
Recently, in vivo study has investigated the level of EMT markers in the gingival tissues of periodontitis patients. It was found that the expression of E-cadherin was downregulated while vimentin expression was upregulated.
Despite the similarities and differences between the pathogenesis of periodontal and peri-implant diseases, the role of dental biofilm in the etiopathogenesis of the aforementioned diseases was studied largely. While it is now accepted that EMT may potentially play a role in periodontal disease pathogenicity, the possible role of EMT in the disintegration of the peri-implant epithelial barrier and the pathogenesis of peri-implant disease has not yet been investigated.
详细描述
Dental implant therapy is a reliable treatment for replacing missing or lost teeth. Despite its high survival and success rates, it has long been realized that biological complications could occur in osseointegrated implants, collectively termed peri-implant diseases. Peri-implantitis is the second most common form of peri-implant disease, and its prevalence was shown to be 10% to 30% at the implant level and 20% at the patient level.
Peri-implantitis is an inflammation of bacterial etiology characterized by inflammation of mucous membranes and bone loss around the dental implant. Clinically, it shows signs of inflammation, bleeding on probing and/or suppuration, increased probing depths, and/or recession of the mucosal margin in addition to radiographic bone loss compared to previous examinations.
Inflammatory peri-implant lesions usually start due to the accumulation of bacterial plaque and progress in a faster pattern compared to periodontitis.
It has been reported that specific dental plaque bacteria could stimulate host cells, including the junctional epithelium, to secrete a range of pro-inflammatory cytokines involved in initiating the epithelial-mesenchymal transition (EMT) process. EMT has been described as the transdifferentiation of epithelial cells into motile mesenchymal cells. It is considered integral in the development, wound healing, and stem cell behavior and contributes pathologically to fibrosis and cancer progression.
Moreover, cytokines and bacterial products have been highlighted as EMT-predisposing factors. It has been proposed that the EMT process could render epithelial cells to lose their cell-cell adhesion and cell polarity that lend these cells to lose their function as an integrated epithelial barrier. Consequently, bacterial invasion into the underlying connective tissues could occur, and epithelial cells are assumed to have a mesenchymal cell phenotype through the upregulation of mesenchymal markers and downregulation of epithelial markers.
研究设计
- 研究类型
- Observational
- 观察模型
- Case Control
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •For test group: adult patient age ≥18 years old presented having at least one dental implant with the following criteria for test group 1: (a) be in function for >12 months; (b) clinically diagnosed as peri-implantitis with probing pocket depth ≥ 6 mm, bleeding on probing and/or suppuration; (c) presence of radiographic bone loss when compared to previous radiographs or with bone loss ≥ 3 mm apical to the 1st thread of the fixture; (d) presence of visual signs of inflammation.
- •For the control group: adult patient age ≥18 years old presented with: (a) one or more adjacent missing teeth in the posterior maxilla or mandible (positions premolar to molar); (b) adequate bone quality and availability for an implant placement of 4.5- 5.0 mm diameter and 8.5-13 mm length; (c) keratinized mucosa (KT) width of at least 3 mm.
- •for both groups the patients give written consent to participate and attend the planned follow-up visits
排除标准
- •For the test group: the exclusion criteria will be as follows: (a) patients with a history of chronic diseases such as diabetes mellitus; (b) currently smokers; (c) pregnant or lactating women; (d) patients who received peri-implant surgical therapy within 6 months before sampling; (e) patients who received antimicrobial therapy (systemic or local) within 3 months before sampling.
- •For the control group: the exclusion criteria will be as follows: (a) medical condition contraindicating implant surgery; (b) local inflammation (including untreated periodontitis); (c) post-extraction sites with less than 6 weeks of healing; (d) persistent intraoral infection; (e) absence of keratinized tissue; (f) history of chronic diseases such as diabetes mellitus; (g) currently a smoker and former smoker
结局指标
主要结局
Peri-implant probing pocket depth (PPD)
时间窗: Measured at baseline just before performing peri-implant tissue harvesting.
PPD is the distance (in mm) measured from the Peri-implant mucosal margin to the base of the peri-implant sulcus/ pocket measured by using a periodontal probe, recorded at six sites per implant namely; mesio-facial, mid-facial, disto-facial, mesio-oral, mid-oral and disto-oral.
Radiographic bone level (RBL)
时间窗: Measured at baseline just before performing peri-implant tissue harvesting.
RBL is the distance (in mm) measured by periapical digital radiograph using the long-cone parallel technique from the implant platform to the radiographic bone level.
Immunohistochemical expression of EMT-related markers
时间窗: Measured at baseline
Immunohistochemical expressions of two EMT-related markers (E-cadherin and vimentin) in peri-implant soft tissue samples collected from patients with peri-implantitis and healthy peri-implant tissue will be measured.
次要结局
- Bleeding on probing (BOP)(Measured at baseline just before performing peri-implant tissue harvesting.)
- Immunohistochemical expression EMT transcriptional factor(Measured at baseline)
研究者
Talib Ali Karam Alnajaty
Principal Investigator
University of Baghdad