Role of toll-like receptor 2 in inflammation and alveolar bone loss in experimental peri-implantitis versus periodontitis.
Role of toll-like receptor 2 in inflammation and alveolar bone loss in experimental peri-implantitis versus periodontitis.
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DOI：
10.1111/jre.12492
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发表时间：
2018-03
影响因子：
3.5
通讯作者：
Han X
中科院分区：
文献类型：
--
作者：
Yu X;Hu Y;Freire M;Yu P;Kawai T;Han X
种植体周围炎和牙周炎虽然在临床和放射学上有相似的特征，但在免疫学上是不同的。Toll样受体2（TLR 2）是先天免疫系统中识别病原体的关键受体之一，在牙周炎的发生、发展过程中起着重要作用。然而，TLR 2在种植体周围炎中的作用仍不清楚。本研究的目的是研究TLR 2在结扎诱导的种植体周围炎小鼠模型中的炎症和牙槽骨丢失中的作用，并将其与结扎诱导的牙周炎进行比较。拔牙后6周，将光滑表面钛种植体放置在野生型（WT）和TLR 2敲除（KO）小鼠左上颌磨牙的牙槽骨中。在种植体放置4周后，将丝线结扎应用于左侧种植体固定装置和右侧上颌第二磨牙，以诱导种植体周围炎和牙周炎。结扎后2周，分别通过微型计算机断层扫描（micro-CT）、组织学和TRAP染色分析种植体和上颌第二磨牙周围的骨丢失和炎症。采用实时定量PCR（RT-qPCR）检测牙龈组织中促炎细胞因子（IL-1β、TNF-α）、抗炎细胞因子（IL-10）和破骨细胞生成相关细胞因子（RANKL、OPG）的mRNA表达。与WT小鼠（53.66%）相比，TLR 2 KO小鼠（85.71%）的植入物骨整合成功率（SR）显著更高（p = 0.0125）。Micro-CT显示，与WT小鼠相比，TLR 2 KO小鼠的种植体周围炎骨丢失显著减少（p = 0.0094）。与对照组相比，WT小鼠种植体周围炎组织中IL-1β（p = 0.0055）、TNF-α（p = 0.01）和IL-10（p = 0.0019）的牙龈mRNA表达显著升高，但在TLR 2 KO小鼠中则无此现象。然而，在WT（p = 0.0488）和TLR 2 KO小鼠（p = 0.0314）中，种植体周围组织中RANKL/OPG的牙龈mRNA比率均显著上调。结扎诱导的牙周炎在骨丢失和炎性细胞因子谱方面表现出相似的模式，除了IL-10水平升高（p = 0.0114），而与对照相比，TLR 2 KO小鼠中RANKL/OPG比率没有升高（p=0.9755）。组织学结果显示，在WT（p<0.01）和TLR 2 KO小鼠（p<0.05）中，结扎诱导的种植体周围炎中出现TRAP阳性细胞和浸润的炎性细胞增加，WT小鼠中的TRAP阳性细胞和浸润的炎性细胞均显著大于TLR 2 KO小鼠。这项研究表明，TLR 2介导种植体周围炎和牙周炎的骨丢失。然而，这两种疾病的发病机制可能存在不同的分子特征。
Peri-implantitis and periodontitis are different entities in immune characteristics even though they share similar features in clinical and radiologic signs. Toll-like receptor 2 (TLR2), one of the key pathogen recognition receptors in the innate immune system, plays an important role in the progress of periodontitis. However, the role of TLR2 in peri-implantitis remains unclear. The objective of this study was to investigate the role of TLR2 in inflammation and alveolar bone loss in a murine model of ligature-induced peri-implantitis and to compare it to ligature-induced periodontitis. Smooth-surface titanium implants were placed in the alveolar bone of the left maxillary molars of Wild Type (WT) and TLR2 knockout (KO) mice 6 weeks after tooth extraction. Silk ligatures were applied to the left implant fixtures and the right maxillary second molars to induce peri-implantitis and periodontitis 4 weeks after implant placement. Bone loss and inflammation around the implants and maxillary second molars were analyzed by micro-computed tomography (micro-CT) and histology and TRAP staining respectively 2 weeks after ligation. Gingival mRNA expressions of pro-inflammatory cytokines (IL-1β, TNF-α), anti-inflammatory cytokine (IL-10) and osteoclastogenesis-related cytokines (RANKL, OPG) were evaluated using real-time quantitative PCR (RT-qPCR). Success Rate (SR) of Implant osseointegration was significantly greater in TLR2 KO mice (85.71%) when compared to WT mice (53.66%) (p = 0.0125). Micro-CT revealed significantly decreased bone loss in TLR2 KO mice as compared to WT mice (p = 0.0094) in peri-implantitis. Gingival mRNA expressions of IL-1β (p = 0.0055), TNF-α (p = 0.01) and IL-10 (p = 0.0019) was significantly elevated in the peri-implantitis tissues of WT mice, but not in TLR2 KO mice, as compared to controls. However, the gingival mRNA ratios of RANKL/OPG in peri-implant tissues were significantly up-regulated in both WT (p = 0.0488) and TLR2 KO mice (p = 0.0314). Ligature-induced periodontitis exhibited the similar patterns in bone loss and inflammatory cytokine profile except that IL-10 level was elevated (p = 0.0114) whereas RANKL/OPG ratio was not elevated (p=0.9755) in TLR2 KO mice compared to control. Histological findings showed increased TRAP-positive cells and infiltrated inflammatory cells presented in ligature-induced peri-implantitis in both WT (p<0.01) and TLR2 KO mice (p<0.05), both of which were significantly greater in WT mice than that in TLR2 KO mice. This study suggests that TLR2 mediates bone loss in both peri-implantitis and periodontitis. However, different molecular features may exist in the pathogenesis of the two diseases.
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