Hippo Signaling Pathway Proteins and Their Correlation With Markers of Apoptosis and Bone Metabolism in the Gingival Crevicular Fluid of Individuals With Periodontal Disease

Inonu University1 个研究点分布在 1 个国家目标入组 75 人开始时间: 2024年1月1日最近更新: 2026年8月13日

适应症

干预措施

试验速览

阶段: 不适用
状态: 已完成
发起方: Inonu University
入组人数: 75
试验地点: 1
主要终点: Gingival crevicular fluid level of Yes-associated protein (YAP)

研究概览研究设计入排标准研究组 & 干预措施结局指标研究者研究点记录与标识符相似试验

研究概览

简要总结

Periodontal disease is a chronic inflammatory condition of the tooth-supporting tissues in which the host inflammatory response drives the destruction of alveolar bone and periodontal attachment. The Hippo signaling pathway is a conserved regulatory network that controls cell proliferation, apoptosis, and bone homeostasis, but its role in human periodontal disease remains unknown. This observational, case-control study compared the levels of Hippo signaling pathway proteins (YAP, TAZ, MST1, TEAD, LATS1, MAP4K4), the anti-apoptotic protein BCL-2, and the bone metabolism marker alkaline phosphatase (ALP) in gingival crevicular fluid across 75 systemically healthy participants grouped as periodontally healthy, gingivitis, or stage 3 grade B periodontitis. The aim was to determine whether these proteins are differentially expressed across periodontal health and disease states and whether they correlate with markers of apoptosis and bone metabolism.

详细描述

Background and rationale

Periodontal disease is a common infectious and inflammatory condition of the periodontium, presenting clinically as gingivitis or periodontitis. Gingivitis is a reversible inflammation confined to the gingiva, whereas periodontitis is a chronic, progressive disease characterized by irreversible loss of periodontal attachment and alveolar bone. Although microbial biofilms containing periodontal pathogens initiate the disease, its severity and progression are largely governed by the host immune-inflammatory response.

The Hippo signaling pathway is a highly conserved regulatory network that integrates mechanical and biochemical cues to control cellular polarity, differentiation, proliferation, apoptosis, immune responses, tissue homeostasis, and organ size. Its core components include Yes-associated protein (YAP), transcriptional co-activator with PDZ-binding motif (TAZ), mammalian sterile 20-like kinase 1 (MST1), TEA domain family members (TEAD), large tumor suppressor kinase 1 (LATS1), and mitogen-activated protein kinase kinase kinase kinase 4 (MAP4K4). Upstream kinases such as MST1/2 and MAP4K4 activate LATS1/2, which phosphorylate YAP and TAZ, leading to their cytoplasmic retention or degradation and preventing TEAD-mediated transcriptional activity in the nucleus.

Preclinical evidence has implicated this pathway in mineralized tissue homeostasis of the alveolar bone and periodontal complex. Inhibition of YAP has been reported to suppress proliferation and induce apoptosis of periodontal ligament stem cells through the BCL-2 family pathway, and YAP/TAZ-deficient animal models show enhanced resorption of alveolar bone and cementum together with reduced alkaline phosphatase expression. Despite these findings, no study to date has directly evaluated the role of Hippo pathway proteins in human periodontal disease. This study was therefore designed to address that gap.

Objective and hypothesis

研究设计

研究类型: Observational
观察模型: Case Control
时间视角: Cross Sectional

入排标准

年龄范围: 18 Years 至 65 Years（Adult, Older Adult）
性别: All
接受健康志愿者: 是

入选标准

•Systemically healthy individuals aged 18-65 years
•Non-smokers or smoking cessation more than 5 years ago
•Healthy group: No history of periodontal disease, ≥20 teeth, probing depth (PD) ≤3 mm at all sites, bleeding on probing (BOP) <10%, radiographic CEJ-to-alveolar bone crest distance ≤3 mm in ≥95% of teeth
•Gingivitis group: No history of periodontal disease, ≥20 teeth, PD ≤3 mm at all sites, BOP ≥30%, radiographic CEJ-to-alveolar bone crest distance ≤3 mm in ≥95% of teeth
•Periodontitis group: ≥15 teeth, >30% of teeth affected by periodontal disease, PD ≥6 mm, clinical attachment loss (CAL) ≥5 mm, vertical bone loss ≥3 mm, Class II or III furcation involvement, radiographic alveolar bone loss extending to the middle third or beyond (≥33%), bone loss-to-age ratio between 0.25 and 1.00

排除标准

•Periodontal treatment or antibiotic use within the past 6 months
•Fewer than 20 teeth (excluding third molars)
•Presence of any systemic disease
•Current smoking or cessation within the past 5 years
•Use of immunosuppressive medication
•Alcohol consumption
•Regular medication use
•Pregnancy or lactation
•Need for antibiotic prophylaxis prior to dental procedures
•Prosthetic restorations on the teeth selected for sampling

研究组 & 干预措施

Periodontally healthy

Systemically healthy adults with clinically healthy periodontium, defined by probing depth of 3 mm or less, bleeding on probing below 10 percent, no clinical attachment loss, and no radiographic bone loss. Gingival crevicular fluid was collected from non-inflamed sites.

干预措施: ELISA Biomarker Analysis (Diagnostic Test)

Gingivitis

Systemically healthy adults with gingival inflammation without attachment loss, defined by probing depth of 3 mm or less, generalized bleeding on probing above 30 percent, no clinical attachment loss, and no radiographic bone loss. Gingival crevicular fluid was collected from inflamed sites.

干预措施: ELISA Biomarker Analysis (Diagnostic Test)

Stage 3 grade B periodontitis

Systemically healthy adults with stage 3 grade B periodontitis, defined by probing depth of 6 mm or more, clinical attachment loss of 5 mm or more, bleeding on probing of 30 percent or more, and radiographic alveolar bone loss extending to the middle or apical third of the root. Gingival crevicular fluid was collected from diseased sites.

干预措施: ELISA Biomarker Analysis (Diagnostic Test)