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奥硝唑调节人牙髓细胞的炎症反应和牙源性分化。

Ornidazole Regulates Inflammatory Response and Odontogenic Differentiation of Human Dental Pulp Cells.

作者信息

Yang Jing, Li Zikai, Zhang Chengcheng, Xiong Jiaying, Yang Xirui, Zheng Dandan, Xie Siming, Shi Haishan

机构信息

School of Stomatology, Jinan University, Guangzhou, China; Department of stomatology, The 924th Hospital of the Joint Logistics Support Force of the People's Liberation Army, Guilin, China.

School of Stomatology, Jinan University, Guangzhou, China.

出版信息

Int Dent J. 2025 Jun;75(3):1522-1531. doi: 10.1016/j.identj.2025.02.008. Epub 2025 Mar 22.

Abstract

AIM

This study aimed to explore the potential of ornidazole as an alternative treatment for pulpitis, focusing on its effects on human dental pulp cells (hDPCs) and macrophages. We assessed the cytotoxicity of various concentrations of ornidazole, its safety and efficacy in treating inflamed hDPCs, and its regulatory impact on inflammatory markers during inflammation.

MATERIALS AND METHODS

Inflammation in hDPCs was induced using lipopolysaccharides (LPS), and varying doses of ornidazole were introduced. Cell proliferation, migration, inflammation regulation, and dentinogenesis under inflammatory conditions were evaluated. Additionally, macrophages were cultured with different doses of ornidazole to analyse the expression of inflammatory genes. If statistically significant differences were observed between the control and treatment groups, this was considered evidence of ornidazole's effects on hDPCs. Statistical analysis was performed using SPSS 26.0, with one-way analysis of variance and Tukey's test for comparisons. A P-value of < 0.05 was considered statistically significant.

RESULTS

Ornidazole influenced cell proliferation, inflammation regulation, and dentinogenesis. Concentrations below 10 µg/mL did not exhibit significant cytotoxic effects on hDPCs over a 7-day period, and the cytotoxicity of ornidazole was both concentration- and time-dependent. Ornidazole decreased the expression of proinflammatory markers (IL-6 and TNF-α) while enhancing the expression of anti-inflammatory markers (IL-1Ra and IL-8). It also suppressed alkaline phosphatase (ALP) activity but increased the expression of odontogenic differentiation markers at both mRNA and protein levels in the presence of inflammatory stimuli. Furthermore, ornidazole demonstrated immunomodulatory effects on macrophages.

CONCLUSIONS

Low concentrations of ornidazole were found to be safe for hDPCs. Ornidazole modulated the expression of inflammatory markers (IL-6, TNF-α, IL-8, IL-1Ra) in inflamed hDPCs and regulated odontogenesis-related markers. Furthermore, low concentrations of ornidazole enhanced the immune regulation in macrophages, highlighting its potential as a therapeutic agent for pulpitis.

CLINICAL RELEVANCE

This study aimed to understand the interactions of ornidazole with hDPCs, its anti-inflammatory properties, and its regulatory effects on odontogenic processes. By examining the impact of different concentrations of ornidazole on cells associated with pulp inflammation, this study provides valuable insights into its therapeutic potential for pulpitis and tends to support its clinical application.

摘要

目的

本研究旨在探索奥硝唑作为牙髓炎替代治疗方法的潜力,重点关注其对人牙髓细胞(hDPCs)和巨噬细胞的影响。我们评估了不同浓度奥硝唑的细胞毒性、其治疗炎症性hDPCs的安全性和有效性,以及其在炎症过程中对炎症标志物的调节作用。

材料与方法

使用脂多糖(LPS)诱导hDPCs发生炎症,并引入不同剂量的奥硝唑。评估炎症条件下的细胞增殖、迁移、炎症调节和牙本质形成。此外,用不同剂量的奥硝唑培养巨噬细胞,以分析炎症基因的表达。如果在对照组和治疗组之间观察到统计学上的显著差异,则认为这是奥硝唑对hDPCs有作用的证据。使用SPSS 26.0进行统计分析,采用单因素方差分析和Tukey检验进行比较。P值<0.05被认为具有统计学意义。

结果

奥硝唑影响细胞增殖、炎症调节和牙本质形成。在7天内,浓度低于10μg/mL的奥硝唑对hDPCs未表现出明显的细胞毒性,且奥硝唑的细胞毒性具有浓度和时间依赖性。奥硝唑降低了促炎标志物(IL-6和TNF-α)的表达,同时增强了抗炎标志物(IL-1Ra和IL-8)的表达。在存在炎症刺激的情况下,它还抑制了碱性磷酸酶(ALP)活性,但在mRNA和蛋白质水平上增加了牙源性分化标志物的表达。此外,奥硝唑对巨噬细胞表现出免疫调节作用。

结论

发现低浓度的奥硝唑对hDPCs是安全的。奥硝唑调节炎症性hDPCs中炎症标志物(IL-6、TNF-α、IL-8、IL-1Ra)的表达,并调节与牙本质形成相关的标志物。此外,低浓度的奥硝唑增强了巨噬细胞中的免疫调节,突出了其作为牙髓炎治疗剂的潜力。

临床意义

本研究旨在了解奥硝唑与hDPCs的相互作用、其抗炎特性以及对牙源性过程的调节作用。通过研究不同浓度奥硝唑对与牙髓炎症相关细胞的影响,本研究为其治疗牙髓炎的潜力提供了有价值的见解,并倾向于支持其临床应用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/02a8/11982462/64adb48fb3af/gr1.jpg

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