Cannabidiol alleviates LPS-inhibited odonto/osteogenic differentiation in human dental pulp stem cells in vitro

IF 7.1 1区医学 Q1 DENTISTRY, ORAL SURGERY & MEDICINE International endodontic journal Pub Date : 2024-12-19 DOI:10.1111/iej.14183

Chatvadee Kornsuthisopon, Ajjima Chansaenroj, Ravipha Suwittayarak, Suphalak Phothichailert, Khunakon Usarprom, Apicha Srikacha, Sornkanok Vimolmangkang, Chaloemrit Phrueksotsai, Lakshman P. Samaranayake, Thanaphum Osathanon

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Abstract

Aim

Cannabidiol (CBD), derived from the Cannabis sativa plant, exhibits benefits in potentially alleviating a number of oral and dental pathoses, including pulpitis and periodontal diseases. This study aimed to explore the impact of CBD on several traits of human dental pulp stem cells (hDPSC), such as their proliferation, apoptosis, migration and odonto/osteogenic differentiation.

Methodology

hDPSCs were harvested from human dental pulp tissues. The cells were treated with CBD at concentrations of 1.25, 2.5, 5, 10, 25 and 50 μg/mL. Cell responses in terms of cell proliferation, colony-forming unit, cell cycle progression, cell migration, apoptosis and odonto/osteogenic differentiation of hDPSCs were assessed in the normal culture condition and P. gingivalis lipopolysaccharide (LPS)-induced ‘inflammatory’ milieus. RNA sequencing and proteomic analysis were performed to predict target pathways impacted by CBD.

Results

CBD minimally affects hDPSCs' behaviour under normal culture growth milieu in normal conditions. However, an optimal concentration of 1.25 μg/mL CBD significantly countered the harmful effects of LPS, indicated by the promoting cell proliferation and restoring the odonto/osteogenic differentiation potential of hDPSCs under LPS-treated conditions. The proteomic analysis demonstrated that several proteins involved in cell proliferation and differentiation were upregulated following CBD exposure, including CCL8, CDC42 and KFL5. RNA sequencing data indicated that CBD upregulated the Notch signalling pathway. In an inhibitory experiment, DAPT, a Notch inhibitor, reduced the effect of CBD-rescued LPS-attenuated mineralization in hDPSCs, suggesting that CBD potentially mediates Notch activation to exert its impact on odonto/osteogenic differentiation of hDPSCs.

Conclusions

CBD recovers the proliferation and survival of hDPSCs following exposure to LPS. Additionally, we report that CBD-mediated Notch activation effectively restores the odonto/osteogenic differentiation ability of hDPSCs under inflamed conditions. These results underscore the potential role of CBD as a therapeutic option to enhance dentine regeneration.

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大麻二酚缓解lps抑制的人牙髓干细胞体外成牙/成骨分化。

目的：大麻二酚（CBD），从大麻植物中提取，在潜在缓解一些口腔和牙齿疾病，包括牙髓炎和牙周病方面表现出益处。本研究旨在探讨CBD对人牙髓干细胞（hDPSC）增殖、凋亡、迁移和成牙/成骨分化等特性的影响。方法：从人牙髓组织中获取hdpsc。分别用浓度为1.25、2.5、5、10、25和50 μg/mL的CBD处理细胞。在正常培养条件和牙龈假单胞菌脂多糖（LPS）诱导的“炎症”环境下，评估hdpsc的细胞增殖、集落形成单位、细胞周期进展、细胞迁移、细胞凋亡和牙/成骨分化方面的细胞反应。通过RNA测序和蛋白质组学分析预测CBD影响的靶标通路。结果：在正常条件下，CBD对hdpsc在正常培养生长环境下的行为影响最小。然而，当CBD浓度为1.25 μg/mL时，可以明显抵消LPS的有害影响，这表明在LPS处理的条件下，CBD可以促进hdpsc的细胞增殖，恢复其向牙/成骨分化的潜力。蛋白质组学分析表明，暴露于CBD后，参与细胞增殖和分化的几种蛋白质上调，包括CCL8、CDC42和KFL5。RNA测序数据表明，CBD上调了Notch信号通路。在一项抑制实验中，Notch抑制剂DAPT降低了CBD拯救的lps在hdpsc中减弱矿化的作用，这表明CBD可能介导Notch激活，从而对hdpsc的齿状/成骨分化产生影响。结论：CBD可恢复LPS暴露后hdpsc的增殖和存活。此外，我们报道了cbd介导的Notch激活有效地恢复了hdpsc在炎症条件下的成牙/成骨分化能力。这些结果强调了CBD作为一种促进牙本质再生的治疗选择的潜在作用。

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来源期刊

International endodontic journal 医学-牙科与口腔外科

CiteScore

10.20

自引率

28.00%

发文量

195

审稿时长

4-8 weeks

期刊介绍： The International Endodontic Journal is published monthly and strives to publish original articles of the highest quality to disseminate scientific and clinical knowledge; all manuscripts are subjected to peer review. Original scientific articles are published in the areas of biomedical science, applied materials science, bioengineering, epidemiology and social science relevant to endodontic disease and its management, and to the restoration of root-treated teeth. In addition, review articles, reports of clinical cases, book reviews, summaries and abstracts of scientific meetings and news items are accepted. The International Endodontic Journal is essential reading for general dental practitioners, specialist endodontists, research, scientists and dental teachers.