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

牙髓干细胞 大麻酚 细胞生物学 细胞生长 细胞凋亡 干细胞 下调和上调 化学 小干扰RNA 成牙骨质细胞 生物 牙骨质 细胞培养 牙科 医学 转染 生物化学 大麻 精神科 遗传学 牙本质 基因
作者
Chatvadee Kornsuthisopon,Ajjima Chansaenroj,Ravipha Suwittayarak,Suphalak Phothichailert,Khunakon Usarprom,Apicha Srikacha,Sornkanok Vimolmangkang,Chaloemrit Phrueksotsai,Lakshman P. Samaranayake,Thanaphum Osathanon
出处
期刊:International Endodontic Journal [Wiley]
被引量:1
标识
DOI:10.1111/iej.14183
摘要

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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