Combined Cannabidiol and Δ9-Tetrahydrocannabinol Modulate Inflammation and Nociceptive Signaling in Human Dental Pulp Cells.

IF 3.9 2区 医学 Q1 DENTISTRY, ORAL SURGERY & MEDICINE
Zar Chi Soe, Daneeya Na Nan, Rahman Wahyudi, Kanokwan Sriwattanapong, Thantrira Porntaveetus, Soranun Chantarangsu, Paksinee Kamolratanakul, Vincent Everts, Chatvadee Kornsuthisopon, Thanaphum Osathanon, Sornkanok Vimolmangkang, Nuttapol Limjeerajarus, Chalida Nakalekha Limjeerajarus
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引用次数: 0

Abstract

Introduction: Dental pulp inflammation, caused by caries, trauma, or restorative operations, produces pain and slows regeneration. Cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC), cannabinoids of Cannabis sativa, have effects on inflammation and pain relief. However, the impact of these factors on dental pulp healing is not yet understood. This study investigated the combined effects of CBD and THC in controlling inflammation and nociception during dental pulp repair.

Methods: Human dental pulp cells were stimulated with lipopolysaccharide and treated with CBD (2.5 μg/mL), THC (0.6 μg/mL), and their combination. Pro-inflammatory cytokines (interleukin [IL]-6, IL-12, and IL-1β) and anti-inflammatory cytokine IL-10 were analyzed using qPCR and enzyme-linked immunosorbent assay, while anti-nociceptive markers (cannabinoid receptor type 1, cannabinoid receptor type 2, and transient receptor potential vanilloid 1) were evaluated by qPCR and Western blot. Cell viability, proliferation, and migration assays were performed to evaluate treatment effects on cellular behaviors associated with pulpal repair and regenerative potential.

Results: Compared with either treatment alone, the CBD/THC combination more effectively attenuated pro-inflammatory cytokines IL-6, IL-12, and IL-1β, enhanced cannabinoid receptor type 1 and cannabinoid receptor type 2 expression, modulated transient receptor potential vanilloid 1, and increased IL-10 expression. Viability assays determined optimal non-cytotoxic concentrations for treatment. The combination enhanced cell proliferation and migration, promoted mineralized nodule formation, and significantly upregulated markers associated with tissue repair, odontogenic differentiation (dentin matrix protein 1), and angiogenesis (vascular endothelial growth factor and basic fibroblast growth factor).

Conclusion: Combined CBD and THC show promise for promoting dental pulp healing by modulating inflammation and nociceptive signaling, while supporting odontogenic differentiation, angiogenesis, and cell migration in human dental pulp cells. These findings provide in vitro evidence supporting combined cannabinoid treatment as a therapeutic strategy for vital pulp therapies.

联合大麻二酚和Δ9-Tetrahydrocannabinol调节人牙髓细胞的炎症和伤害性信号。
牙髓炎症是由蛀牙、外伤或修复手术引起的,会产生疼痛并减缓牙髓再生。大麻二酚(CBD)和Δ9-tetrahydrocannabinol (THC)是大麻中的大麻素,对炎症和疼痛有缓解作用。然而,这些因素对牙髓愈合的影响尚不清楚。本研究探讨了CBD和四氢大麻酚在牙髓修复过程中对炎症和伤害感觉的控制作用。方法:用脂多糖(LPS)刺激人牙髓细胞,用CBD (2.5 μg/mL)、四氢大麻酚(0.6 μg/mL)及其联合处理。采用qPCR和ELISA检测促炎因子(IL-6、IL-12和IL-1β)和抗炎因子IL-10,采用qPCR和Western blot检测抗伤害标志物(CNR1、CNR2和TRPV1)。通过细胞活力、增殖和迁移试验来评估治疗对与牙髓修复和再生潜能相关的细胞行为的影响。结果:与单独治疗相比,CBD/THC联合治疗更有效地减弱了促炎细胞因子IL-6、IL-12和IL-1β,增强了CNR1和CNR2的表达,调节了TRPV1,增加了IL-10的表达。活力测定确定治疗的最佳非细胞毒性浓度。联合治疗可增强细胞增殖和迁移,促进矿化结节形成,并显著上调与组织修复、牙源性分化(DMP1)和血管生成(VEGF和bFGF)相关的标志物。结论:大麻二酚和四氢大麻酚联用可通过调节炎症和伤害性信号传导促进牙髓愈合,同时支持牙髓细胞成牙分化、血管生成和细胞迁移。这些发现提供了体外证据,支持大麻素联合治疗作为重要牙髓治疗的治疗策略。
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来源期刊
Journal of endodontics
Journal of endodontics 医学-牙科与口腔外科
CiteScore
8.80
自引率
9.50%
发文量
224
审稿时长
42 days
期刊介绍: The Journal of Endodontics, the official journal of the American Association of Endodontists, publishes scientific articles, case reports and comparison studies evaluating materials and methods of pulp conservation and endodontic treatment. Endodontists and general dentists can learn about new concepts in root canal treatment and the latest advances in techniques and instrumentation in the one journal that helps them keep pace with rapid changes in this field.
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