Kornsuthisopon Chatvadee, Chansaenroj Ajjima, Suwittayarak Ravipha, Phothichailert Suphalak, Usarprom Khunakon, Srikacha Apicha, Vimolmangkang Sornkanok, Phrueksotsai Chaloemrit, Samaranayake Lakshman P, Osathanon Thanaphum
Department of Anatomy, Faculty of Dentistry, Chulalongkorn University, Bangkok, Thailand.
Center of Excellence for Dental Stem Cell Biology, Faculty of Dentistry, Chulalongkorn University, Bangkok, Thailand.
Int Endod J. 2025 Mar;58(3):449-466. doi: 10.1111/iej.14183. Epub 2024 Dec 19.
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.
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.
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.
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.
大麻二酚（CBD）源自大麻植物，在潜在缓解多种口腔和牙科病症方面显示出益处，包括牙髓炎和牙周疾病。本研究旨在探讨CBD对人牙髓干细胞（hDPSC）若干特性的影响，如增殖、凋亡、迁移以及成牙本质/成骨分化。
从人牙髓组织中获取hDPSC。细胞用浓度为1.25、2.5、5、10、25和50μg/mL的CBD处理。在正常培养条件和牙龈卟啉单胞菌脂多糖（LPS）诱导的“炎症”环境中评估hDPSC在细胞增殖、集落形成单位、细胞周期进程、细胞迁移、凋亡以及成牙本质/成骨分化方面的细胞反应。进行RNA测序和蛋白质组分析以预测受CBD影响的靶途径。
在正常条件下的正常培养生长环境中，CBD对hDPSC的行为影响极小。然而，1.25μg/mL的最佳CBD浓度显著对抗了LPS的有害影响，这表现为在LPS处理条件下促进hDPSC的细胞增殖并恢复其成牙本质/成骨分化潜能。蛋白质组分析表明，暴露于CBD后，几种参与细胞增殖和分化的蛋白质上调，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挽救的LPS减弱的hDPSC矿化作用，表明CBD可能介导Notch激活以对hDPSC的成牙本质/成骨分化产生影响。
CBD在hDPSC暴露于LPS后恢复其增殖和存活能力。此外，我们报告CBD介导的Notch激活在炎症条件下有效恢复hDPSC的成牙本质/成骨分化能力。这些结果强调了CBD作为增强牙本质再生治疗选择的潜在作用。
