Xi Xun, Li Zi-Xuan, Zhao Yi, Liu Hong, Chen Shuai, Liu Dong-Xu
School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China.
Shandong Key Laboratory of Oral Tissue Regeneration, Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration, Jinan, Shandong, China.
J Dent Sci. 2022 Apr;17(2):750-762. doi: 10.1016/j.jds.2021.10.003. Epub 2021 Oct 28.
BACKGROUND/PURPOSE: Mechanical stress plays a vital role in osteogenic differentiation of periodontal ligament stem cells (PDLSCs). Cyclic mechanical stress may up-regulate reactive oxygen species (ROS) level. N-acetylcysteine (NAC) possesses powerful antioxidant capacity. However, it is undefined the impact of NAC on osteogenic differentiation stimulated by cyclic mechanical stress in PDLSCs. The aim of our research was to study the effect of NAC on PDLSCs during osteogenic differentiation under cyclic mechanical stress.
The expression levels of osteogenesis markers were used to examine the osteogenic differentiation of PDLSCs. ROS production were measured by flow cytometry. The levels of reduced glutathione (GSH) and oxidized glutathione (GSSG) were analyzed. We also examined the changes of alveolar bone and periodontal ligament (PDL) tissues in orthodontic rats by micro-computed tomography (micro-CT) system and immunohistochemistry (IHC) staining. The nuclear factor erythroid-2-related factor-2 (Nrf2) expression was examined.
NAC could enhance the osteogenic differentiation and up-regulate the GSH level as well as the ratio of GSH/GSSG, while down-regulate ROS generation and Nrf2 expression induced by cyclic mechanical stress in PDLSCs. NAC had beneficial effects on the microstructure of alveolar bone and enhanced the expression levels of osteogenesis markers, such as alkaline phosphatase (ALP) and collagen type 1 (COL1) in PDL in orthodontic rats at the tension side.
NAC could improve the osteogenic differentiation stimulated by cyclic mechanical stress in PDLSCs and in orthodontic rats, suggesting a potential therapeutic approach for alveolar bone remodeling in orthodontics.
背景/目的：机械应力在牙周膜干细胞（PDLSCs）的成骨分化中起重要作用。周期性机械应力可能上调活性氧（ROS）水平。N-乙酰半胱氨酸（NAC）具有强大的抗氧化能力。然而，NAC对周期性机械应力刺激的PDLSCs成骨分化的影响尚不清楚。我们研究的目的是探讨NAC在周期性机械应力作用下对PDLSCs成骨分化的影响。
用成骨标志物的表达水平检测PDLSCs的成骨分化。通过流式细胞术检测ROS的产生。分析还原型谷胱甘肽（GSH）和氧化型谷胱甘肽（GSSG）的水平。我们还通过微型计算机断层扫描（micro-CT）系统和免疫组织化学（IHC）染色检查正畸大鼠牙槽骨和牙周膜（PDL）组织的变化。检测核因子红细胞2相关因子2（Nrf2）的表达。
NAC可增强PDLSCs的成骨分化，上调GSH水平及GSH/GSSG比值，同时下调周期性机械应力诱导的ROS生成和Nrf2表达。NAC对正畸大鼠张力侧牙槽骨的微观结构有有益影响，并增强了牙周膜中碱性磷酸酶（ALP）和I型胶原（COL1）等成骨标志物的表达水平。
NAC可改善周期性机械应力刺激的PDLSCs和成骨大鼠的成骨分化，提示其可能是正畸中牙槽骨重塑的一种潜在治疗方法。
