State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
Department of Prosthodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
J Periodontal Res. 2021 Aug;56(4):667-678. doi: 10.1111/jre.12863. Epub 2021 Mar 2.
Diabetes accelerates inflammaging in various tissue with an increase in senescent cell burden and senescence-associated secretory phenotype (SASP) secretion, which is a significant cause of tissue dysfunction and contributes to the diabetic complications. Recently, inflammasomes are thought to contribute to inflammaging. Here, utilizing diabetic models in vivo and in vitro, we investigated the potential association between hyperglycemia-induced inflammaging and gingival tissue dysfunction and the mechanism underlying inflammasome-associated inflammaging.
Gingival epithelium and serum were collected from control and diabetic patients and mice. The expression of p16, p21, and inflammasomes in the gingival epithelium, SASP factors in serum, and the molecular factors associated with gingival epithelial barrier function were assessed. Human oral keratinocyte (HOK) was stimulated with normal and high glucose, and pre-treated with Z-YVAD-FMK (Caspase-1 inhibitor) prior to evaluating cellular senescence, SASP secretion, and inflammasome activation.
In vivo, hyperglycemia significantly elevated the local burden of senescent cells in the gingival epithelium and SASP factors in the serum and simultaneously reduced the expression levels of Claudin-1, E-cadherin, and Connexin 43 in the gingival epithelium. Interestingly, the inflammasomes were activated in the gingival epithelium. In vitro, high glucose-induced the inflammaging in HOK, and blocking inflammasome activation through inhibiting Caspase-1 and glucose-induced inflammaging.
Hyperglycemia accelerated inflammaging in the gingival epithelium through inflammasomes activation, which is potentially affiliated with a decline in the gingival epithelial barrier function in diabetes. Inflammasomes-related inflammaging may be the crucial mechanism underlying diabetic periodontitis and represents significant opportunities for advancing prevention and treatment options.
糖尿病会加速各种组织中的炎症衰老，增加衰老细胞负担和衰老相关分泌表型（SASP）的分泌，这是组织功能障碍的一个重要原因，并导致糖尿病并发症。最近，炎症小体被认为与炎症衰老有关。在这里，我们利用体内和体外的糖尿病模型，研究了高血糖诱导的炎症衰老与牙龈组织功能障碍之间的潜在关联，以及炎症小体相关炎症衰老的潜在机制。
收集来自对照和糖尿病患者和小鼠的牙龈上皮和血清。评估牙龈上皮中的 p16、p21 和炎症小体、血清中的 SASP 因子以及与牙龈上皮屏障功能相关的分子因子。用正常和高葡萄糖刺激人口腔角质细胞（HOK），并用 Z-YVAD-FMK（Caspase-1 抑制剂）预处理，然后评估细胞衰老、SASP 分泌和炎症小体激活。
体内，高血糖显著增加了牙龈上皮中衰老细胞的局部负担和血清中的 SASP 因子，同时降低了牙龈上皮中 Claudin-1、E-钙粘蛋白和 Connexin 43 的表达水平。有趣的是，炎症小体在牙龈上皮中被激活。体外，高葡萄糖诱导 HOK 发生炎症衰老，通过抑制 Caspase-1 阻断炎症小体激活可减轻葡萄糖诱导的炎症衰老。
高血糖通过炎症小体激活加速了牙龈上皮的炎症衰老，这可能与糖尿病中牙龈上皮屏障功能下降有关。炎症小体相关的炎症衰老可能是糖尿病性牙周炎的关键机制，并为预防和治疗提供了重要机会。
