Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, College of Stomatology, Xi'an Jiaotong University, Xi'an, Shaanxi, China; Clinical Research Center of Shaanxi Province for Dental and Maxillofacial Diseases, College of Stomatology, Xian Jiaotong University, Xi'an, Shaanxi, China; Department of Cariology and Endodontics, College of Stomatology, Xi'an Jiaotong University, Xi'an, Shaanxi, China.
Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, College of Stomatology, Xi'an Jiaotong University, Xi'an, Shaanxi, China; Clinical Research Center of Shaanxi Province for Dental and Maxillofacial Diseases, College of Stomatology, Xian Jiaotong University, Xi'an, Shaanxi, China; Department of Cariology and Endodontics, College of Stomatology, Xi'an Jiaotong University, Xi'an, Shaanxi, China; Sichuan Hospital of Stomatology, Chengdu, Sichuan, China.
Arch Oral Biol. 2024 Jan;157:105848. doi: 10.1016/j.archoralbio.2023.105848. Epub 2023 Nov 10.
In this study, we investigated the involvement of Gremlin1 on the pathological process of apical periodontitis and detect the underlying mechanisms preliminarily.
Clinical healthy and inflamed periapical specimens were collected. Then, apical periodontitis (AP) animal models were established by consistent pulp exposure. In addition, AAV-shGremlin1 was injected into inflamed periapical lesions to inhibit the expression of Gremlin1. Alveolar bone loss was measured by Micro-CT. Furthermore, immunohistochemical or immunofluorescence staining of Gremlin1, phosphorylated-CREB, ICAM-1, VCAM-1, IL-1β were performed.
The expression of Gremlin1 is markedly increased in periapical lesions not only in clinic samples but also in animal models. Moreover, in rats' AP model, we uncovered that the Gremlin1 protein expression levels in apical lesions is positively correlated with those of IL-1β. Besides, the blockade of Gremlin1 in periapical lesions could substantially suppress the alveolar bone loss and restrains the inflammatory status by impacting the activation levels of phosphorylated-CREB, ICAM-1, VCAM-1, IL-1β.
Taken together, these results illustrated that Gremlin1 acts as a crucial mediator and possibly serves as a potential diagnostic marker for periapical periodontitis. Discovery of new factors involved in the pathophysiology of periapical periodontitis could contribute to the development of novel therapeutic treatment for the disease.
本研究旨在探讨 Gremlin1 在根尖周炎病理过程中的作用,并初步探讨其潜在机制。
收集临床健康和炎症性根尖标本。然后,通过持续牙髓暴露建立根尖周炎(AP)动物模型。此外,将 AAV-shGremlin1 注射到炎症性根尖病变部位以抑制 Gremlin1 的表达。通过 Micro-CT 测量牙槽骨丢失。此外,进行 Gremlin1、磷酸化-CREB、ICAM-1、VCAM-1、IL-1β的免疫组织化学或免疫荧光染色。
不仅在临床样本中,而且在动物模型中,根尖病变中 Gremlin1 的表达明显增加。此外,在大鼠 AP 模型中,我们发现根尖病变中 Gremlin1 蛋白表达水平与 IL-1β呈正相关。此外,在根尖病变中阻断 Gremlin1 可通过影响磷酸化-CREB、ICAM-1、VCAM-1、IL-1β的激活水平,显著抑制牙槽骨丢失和炎症状态。
综上所述,这些结果表明 Gremlin1 作为一种重要的介质,可能作为根尖周炎的潜在诊断标志物。发现参与根尖周炎病理生理学的新因素可能有助于开发该疾病的新治疗方法。