Department of Orthodontics, Center of Dento-Maxillo-Facial Medicine, University of Bonn, Welschnonnenstr, 17 53111, Bonn, Germany.
Section of Experimental Dento-Maxillo-Facial Medicine, Center of Dento-Maxillo-Facial Medicine, University of Bonn, Bonn, Germany.
Head Face Med. 2019 Jan 4;15(1):2. doi: 10.1186/s13005-018-0185-1.
Periodontitis is a chronic disease characterized by a progressive and irreversible destruction of the tooth-supporting tissues, including gingiva and periodontal ligament (PDL). Microorganisms, such as Fusobacterium nucleatum, evoke an inflammatory host response, which leads to increased levels of inflammatory mediators, such as interleukin (IL)-1β. Periodontitis has been linked to obesity, and adipokines have been suggested to represent a pathomechanistic link. The hormone somatostatin (SST) exerts antiproliferative, antiangiogenetic, proapoptotic, anti-nociceptive and other effects through binding to its receptors, such as SSTR2. Therefore, the objective of the present study was to examine the regulation of SSTR2 in periodontal cells and tissues under inflammatory, microbial and obesity-related conditions.
In-vitro, human PDL fibroblasts were exposed to IL-1β, F. nucleatum, leptin or visfatin. The SSTR2 regulation was assessed by real-time PCR and immunocytochemistry. In-vivo, the SSTR2 expression was analyzed in gingival biopsies of periodontally diseased and healthy subjects by real-time PCR and immunohistochemistry. Additionally, the SSTR2 expression was determined in gingival biopsies of rats with ligature-induced periodontitis, rats with diet-induced obesity, and periodontally and systemically healthy control animals. For statistical analyses, the Mann-Whitney-U test and ANOVA with post-hoc tests were applied (p < 0.05).
Exposure of PDL cells to IL-1β and F. nucleatum caused a significant SSTR2 upregulation by 2.6-fold and 6.4-fold, respectively. Additionally, leptin and visfatin increased significantly the SSTR2 gene expression by 3.0-fold and 2.8-fold, respectively. These stimulatory effects were also observed at protein level. SSTR2 expressions in human gingival biopsies from sites of periodontitis were significantly higher than those in healthy biopsies. Similarly, SSTR2 expression levels were significantly enhanced at periodontally-diseased sites in rat experimental periodontitis. Finally, the SSTR2 expression was significantly upregulated in gingival biopsies of obese rats as compared to normal weight control animals.
Our study provides original insights into the SSTR2 regulation in cells and tissues of the periodontium. We demonstrate for the first time that proinflammatory, microbial and obesity-associated molecules result in an SSTR2 upregulation. Since SST has been shown to be antiproliferative, antiangiogenetic, and proapoptotic, our study suggests that SSTR2 might play a critical role in the aetiopathogenesis of periodontitis.
牙周炎是一种慢性疾病，其特征为牙齿支持组织（包括牙龈和牙周韧带）的进行性和不可逆破坏。诸如具核梭杆菌等微生物引发炎症性宿主反应，导致炎症介质（如白细胞介素-1β）水平升高。牙周炎与肥胖有关，并且已提出脂肪细胞因子代表一种发病机制联系。生长抑素（SST）通过与其受体（如 SSTR2）结合，发挥抗增殖、抗血管生成、促凋亡、抗伤害感受等作用。因此，本研究的目的是研究在炎症、微生物和肥胖相关条件下牙周细胞和组织中 SSTR2 的调节。
在体外，将人牙周膜成纤维细胞暴露于白细胞介素-1β、具核梭杆菌、瘦素或内脂素。通过实时 PCR 和免疫细胞化学评估 SSTR2 的调节。在体内，通过实时 PCR 和免疫组织化学分析牙周炎和健康受试者牙龈活检中的 SSTR2 表达。此外，还确定了结扎诱导牙周炎大鼠、饮食诱导肥胖大鼠以及牙周和系统健康对照动物的牙龈活检中的 SSTR2 表达。对于统计分析，应用了曼-惠特尼 U 检验和方差分析（事后检验）（p<0.05）。
PDL 细胞暴露于白细胞介素-1β和具核梭杆菌分别导致 SSTR2 上调 2.6 倍和 6.4 倍。此外，瘦素和内脂素分别使 SSTR2 基因表达显著增加 3.0 倍和 2.8 倍。这些刺激作用也在蛋白质水平上观察到。来自牙周炎部位的人牙龈活检中的 SSTR2 表达明显高于健康活检中的表达。同样，在大鼠实验性牙周炎中，牙周病部位的 SSTR2 表达水平也显著增强。最后，与正常体重对照动物相比，肥胖大鼠的牙龈活检中的 SSTR2 表达明显上调。
本研究为牙周组织中 SSTR2 的调节提供了新的见解。我们首次证明促炎、微生物和肥胖相关分子导致 SSTR2 上调。由于 SST 已显示出抗增殖、抗血管生成和促凋亡作用，因此我们的研究表明 SSTR2 可能在牙周炎的发病机制中发挥关键作用。
