Periodontitis is one of the most prevalent human inflammatory diseases. It is characterized by periodontal tissue destruction, progressively driven by the host response. In this regard, cytokines associated with tissue destruction, such as interleukin (IL)-6 and IL-23, use a common signaling pathway mediated by STAT3. This transcription factor is also needed for IL-17A production, a key mediator in periodontitis pathogenesis. Although several studies have reported increased activation of STAT3 in experimental periodontitis, a detailed characterization of STAT3 activation in human gingival tissues and its involvement in alveolar bone loss has yet to be explored. Using a cross-sectional study design, we detected increased proportions of pSTAT3-positive cells during periodontitis compared with health, particularly in epithelial cells and T cells. Other cell types of hematopoietic and nonhematopoietic origin also display STAT3 activation in gingival tissues. We detected increased STAT3 phosphorylation and expression of STAT3-related genes during experimental periodontitis. Next, we evaluated the role of STAT3 in alveolar bone destruction using a mouse model of STAT3 loss of function (mut-Stat3 mice). Compared with controls, mut-Stat3 mice had reduced alveolar bone loss following ligature-induced periodontitis. We also evaluated pharmacologic inhibition of STAT3 in ligature-induced periodontitis. Like mut-Stat3 mice, mice treated with STAT3 small-molecule inhibitor had reduced bone loss compared with controls. Our results demonstrate that STAT3 activation is increased in epithelial and T cells during periodontitis and indicate a pathogenic role of STAT3 in inflammatory alveolar bone loss.

中文翻译：

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牙周炎中 STAT3 激活增加会导致炎性骨质流失。

牙周炎是人类最常见的炎症性疾病之一。其特征是牙周组织破坏，由宿主反应逐渐驱动。在这方面，与组织破坏相关的细胞因子，例如白细胞介素 (IL)-6 和 IL-23，使用由 STAT3 介导的常见信号通路。IL-17A 的产生也需要这种转录因子，IL-17A 是牙周炎发病机制的关键介质。尽管一些研究报告实验性牙周炎中 STAT3 的激活增加，但人类牙龈组织中 STAT3 激活的详细特征及其与牙槽骨丢失的关系仍有待探索。通过横断面研究设计，我们发现与健康相比，牙周炎期间 pSTAT3 阳性细胞的比例有所增加，尤其是上皮细胞和 T 细胞。其他造血和非造血来源的细胞类型也在牙龈组织中表现出 STAT3 激活。我们检测到实验性牙周炎期间 STAT3 磷酸化和 STAT3 相关基因表达增加。接下来，我们使用 STAT3 功能丧失的小鼠模型（mut-Stat3 小鼠）评估了 STAT3 在牙槽骨破坏中的作用。与对照组相比，mut-Stat3 小鼠在结扎引起的牙周炎后牙槽骨丢失减少。我们还评估了 STAT3 在结扎诱导的牙周炎中的药理学抑制作用。与 mut-Stat3 小鼠一样，与对照组相比，接受 STAT3 小分子抑制剂治疗的小鼠骨质流失减少。我们的结果表明，牙周炎期间上皮细胞和 T 细胞中 STAT3 的激活增加，并表明 STAT3 在炎症性牙槽骨丢失中的致病作用。