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雷公藤内酯醇通过 p-IκBα/NF-κB 信号通路减轻 TNF-α 诱导的人牙周膜干细胞成骨抑制作用:一项体外研究。

Triptolide mitigates the inhibition of osteogenesis induced by TNF-α in human periodontal ligament stem cells via the p-IκBα/NF-κB signaling pathway: an in-vitro study.

机构信息

Department of Orthodontics, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration & Shandong Provincial Clinical Research Center for Oral Diseases, Shandong University, No.44-1 Wenhua Road West, Jinan, 250012, Shandong Province, China.

Science and Technology Innovation Committee of Shenzhen Municipality, Shenzhen Research Institute of Shandong University, A301 Virtual University Park in South District of Shenzhen, Shenzhen, 518063, Guangdong Province, China.

出版信息

BMC Complement Med Ther. 2024 Mar 6;24(1):113. doi: 10.1186/s12906-024-04408-2.

Abstract

BACKGROUND

Triptolide is a widely utilized natural anti-inflammatory drug in clinical practice. Aim of this study was to evaluate effects of triptolide on hPDLSCs osteogenesis in an inflammatory setting and to investigate underlying mechanisms.

METHODS

Using the tissue block method to obtain hPDLSCs from extracted premolar or third molar. Flow cytometry, osteogenic and adipogenic induction were carried out in order to characterise the features of the cells acquired. hPDLSC proliferative activity was assessed by CCK-8 assay to determine the effect of TNF-α and/or triptolide. The impact of triptolide on the osteogenic differentiation of hPDLSCs was investigated by ALP staining and quantification. Osteogenesis-associated genes and proteins expression level were assessed through PCR and Western blotting assay. Finally, BAY-117,082 was used to study the NF-κB pathway.

RESULTS

In the group treated with TNF-α, there was an elevation in inflammation levels while osteogenic ability and the expression of both osteogenesis-associated genes and proteins decreased. In the group co-treated with TNF-α and triptolide, inflammation levels were reduced and osteogenic ability as well as the expression of both osteogenesis-associated genes and proteins were enhanced. At the end of the experiment, both triptolide and BAY-117,082 exerted similar inhibitory effects on the NF-κB pathway.

CONCLUSION

The osteogenic inhibition of hPDLSCs by TNF-α can be alleviated through triptolide, with the involvement of the p-IκBα/NF-κB pathway in this mechanism.

摘要

背景

雷公藤红素是临床实践中广泛应用的天然抗炎药物。本研究旨在评估雷公藤红素在炎症环境下对人牙周膜干细胞成骨的影响,并探讨其潜在机制。

方法

采用组织块法从提取的前磨牙或第三磨牙中获得人牙周膜干细胞。通过流式细胞术、成骨和成脂诱导来鉴定细胞的特征。通过 CCK-8 assay 评估 TNF-α 和/或雷公藤红素对 hPDLSCs 增殖活性的影响。通过 ALP 染色和定量来研究雷公藤红素对 hPDLSCs 成骨分化的影响。通过 PCR 和 Western blot assay 来评估成骨相关基因和蛋白的表达水平。最后,使用 BAY-117,082 研究 NF-κB 通路。

结果

在 TNF-α 处理组中,炎症水平升高,而成骨能力和骨形成相关基因和蛋白的表达降低。在 TNF-α 和雷公藤红素共同处理组中,炎症水平降低,成骨能力以及骨形成相关基因和蛋白的表达增强。实验结束时,雷公藤红素和 BAY-117,082 对 NF-κB 通路均具有相似的抑制作用。

结论

TNF-α 对 hPDLSCs 的成骨抑制作用可以通过雷公藤红素缓解,该机制涉及 p-IκBα/NF-κB 通路。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/88a0/10916329/6cf4b04002c8/12906_2024_4408_Fig1_HTML.jpg

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