Colgate Australian Clinical Dental Research Centre, School of Dentistry, University of Adelaide, Adelaide, SA, Australia.
J Periodontal Res. 2010 Aug;45(4):564-73. doi: 10.1111/j.1600-0765.2010.01275.x. Epub 2010 Jun 10.
Host-derived enzymes, cytokines and other proinflammatory mediators play an integral role in periodontal destruction. The levels of tumor necrosis factor-like weak inducer of apoptosis (TWEAK) and its receptor, fibroblast growth factor-inducible 14 protein (Fn14), are elevated in tissues from a number of chronic inflammatory diseases. The aim of the present study was to investigate the expression of TWEAK and Fn14 at the protein and mRNA levels in gingival biopsies from periodontitis patients and from clinically healthy patients.
Gingival biopsies were obtained from healthy sites (n = 7) and from sites affected by periodontitis (n = 27). The expression of TWEAK and Fn14 was investigated by immunohistochemistry in formalin-fixed, paraffin-embedded tissues. The levels of mRNA for TWEAK and Fn14 were also investigated by RT-PCR.
The expression of TWEAK and Fn14 proteins was significantly higher in periodontitis tissue than in healthy tissue. In periodontitis tissues, TWEAK and Fn14 proteins were mainly expressed by mononuclear leukocytes (morphologically resembling lymphocytes and plasma cells), by cells lining blood vessels, by spindle-shaped cells resembling fibroblasts and by multinucleated cells. The Fn14 mRNA level in periodontitis tissue was significantly higher than that in healthy tissue. A moderate correlation between TWEAK/Fn14 expression and inflammation and bone loss, but not pocket depth, was noted.
This study demonstrates higher expression of TWEAK protein and of Fn14 mRNA and protein in periodontitis tissues than in clinically healthy controls. Our data support the concept that TWEAK/Fn14 signaling is an additional player in the pathogenesis of periodontitis and adds to the increasing number of cytokine networks involved in periodontal inflammation.
宿主来源的酶、细胞因子和其他促炎介质在牙周破坏中起着重要作用。肿瘤坏死因子样凋亡弱诱导剂（TWEAK）及其受体成纤维细胞生长因子诱导 14 蛋白（Fn14）的水平在许多慢性炎症性疾病的组织中升高。本研究旨在探讨 TWEAK 和 Fn14 在牙周炎患者和临床健康患者牙龈活检组织中的蛋白和 mRNA 水平的表达。
从健康部位（n=7）和受牙周炎影响的部位（n=27）获得牙龈活检组织。通过免疫组织化学法在福尔马林固定、石蜡包埋组织中检测 TWEAK 和 Fn14 的表达。还通过 RT-PCR 检测 TWEAK 和 Fn14 的 mRNA 水平。
TWEAK 和 Fn14 蛋白的表达在牙周炎组织中明显高于健康组织。在牙周炎组织中，TWEAK 和 Fn14 蛋白主要由单核白细胞（形态类似于淋巴细胞和浆细胞）、血管衬里细胞、类似成纤维细胞的梭形细胞和多核细胞表达。牙周炎组织中的 Fn14 mRNA 水平明显高于健康组织。TWEAK/Fn14 表达与炎症和骨丢失之间存在中度相关性，但与牙周袋深度无关。
本研究表明，TWEAK 蛋白和 Fn14 mRNA 和蛋白在牙周炎组织中的表达明显高于临床健康对照组。我们的数据支持 TWEAK/Fn14 信号是牙周炎发病机制中的另一个参与者的概念，并增加了涉及牙周炎症的细胞因子网络的数量。
