Department of Endodontics, Affiliated Stomatological Hospital of Fujian Medical University, Fuzhou, Fujian, China.
Fujian Provincial Key Laboratory of Stomatology, Fuzhou, Fujian, China.
Cell Biochem Funct. 2020 Jul;38(5):676-682. doi: 10.1002/cbf.3528. Epub 2020 Apr 1.
Invasion of dentinal tubules and pulp tissue by pathogenic bacteria may cause infection leading to pulpitis. Sirtuin 6 (SIRT6) is a NAD-dependent protein deacetylase encoded by the SIRT6 gene. The effect of SIRT6 on lipopolysaccharide (LPS)-induced pulpitis and its mechanism of action were discussed in this study. Dental pulp cells (DPCs) were extracted from human teeth and injected with LPS to induce inflammation. The cells injected with LPS showed substantially decreased expression of SIRT6. The overexpression of SIRT6, induced by plasmid-transfection of DPCs with SIRT6 overexpressing vector, led to a marked decrease in proinflammatory cytokines (IL-6, IL-1β, and TNF-α) and deactivation of NF kappa B pathway. Additionally, dentin matrix protein-1 (DMP1), a promoter of inflammation in dental pulp tissues, was downregulated. Further investigation revealed that SIRT6 promotes ubiquitination of the transient receptor potential vanilloid 1 (TRPV1) channel, leading to its degradation and deactivation. The role of TRPV1 in the anti-inflammatory effects of SIRT6 was determined through incubation of SIRT6-expressing dental pulp stem cells (DPSCs) with capsaicin. This incubation counteracted the effect of SIRT6 on cytokines and DMP1. The injection of lentivirus-SIRT6 attenuated LPS-induced pulpitis in vivo by suppressing TRPV1 activity. Thus, SIRT6 inhibits the TRPV1 channel during LPS-induced inflammation of dental pulp. SIGNIFICANCE OF THE STUDY: This study discussed the effect of sirtuin 6 (SIRT6) on lipopolysaccharide (LPS)-induced pulpitis as well as its mechanism of action and found that SIRT6 may be a negative regulator of pulpitis. Additionally, low expression of SIRT6 and high expression of transient receptor potential vanilloid 1 (TRPV1) in LPS-treated human dental pulp cells are closely associated with proinflammatory cytokines, dentin matrix protein 1 expression, and activation of the NF-κB pathway, which indicated that TRPV1 may be a biomarker for pulpitis and the SIRT6-TRPV1-CGRP axis maybe a clinical target due to their role regulating inflammation and neuropathic pain.
牙本质小管和牙髓组织被致病菌入侵可能导致感染，进而引发牙髓炎。Sirtuin 6（SIRT6）是一种由 SIRT6 基因编码的 NAD 依赖性蛋白去乙酰化酶。本研究探讨了 SIRT6 对脂多糖（LPS）诱导的牙髓炎的影响及其作用机制。从人牙中提取牙髓细胞（DPC）并注入 LPS 以诱导炎症。注入 LPS 的细胞中 SIRT6 的表达明显降低。通过用 SIRT6 过表达载体转染 DPC 来过表达 SIRT6，导致促炎细胞因子（IL-6、IL-1β和 TNF-α）显著减少和 NF kappa B 途径失活。此外，下调了牙本质基质蛋白 1（DMP1），这是牙髓组织中炎症的启动子。进一步研究表明，SIRT6 促进瞬时受体电位香草酸 1（TRPV1）通道的泛素化，导致其降解和失活。通过用辣椒素孵育 SIRT6 表达的牙髓干细胞（DPSC）来确定 TRPV1 在 SIRT6 的抗炎作用中的作用。这种孵育抵消了 SIRT6 对细胞因子和 DMP1 的作用。LPS 诱导的牙髓炎的体内注射慢病毒-SIRT6 通过抑制 TRPV1 活性来减弱。因此，SIRT6 在 LPS 诱导的牙髓炎症中抑制 TRPV1 通道。研究的意义：本研究讨论了 Sirtuin 6（SIRT6）对脂多糖（LPS）诱导的牙髓炎的影响及其作用机制，并发现 SIRT6 可能是牙髓炎的负调节剂。此外，LPS 处理的人牙髓细胞中 SIRT6 表达降低和瞬时受体电位香草酸 1（TRPV1）表达升高与促炎细胞因子、牙本质基质蛋白 1 表达和 NF-κB 途径激活密切相关，这表明 TRPV1 可能是牙髓炎的生物标志物，SIRT6-TRPV1-CGRP 轴可能是一个临床靶点，因为它们在调节炎症和神经病理性疼痛方面发挥作用。
