Department of Restorative Dentistry, School of Dentistry, University of São Paulo, São Paulo, Brazil.
Department of Endodontics, University of Texas Health Science Center at San Antonio, San Antonio, Texas.
J Endod. 2021 Oct;47(10):1617-1624. doi: 10.1016/j.joen.2021.07.010. Epub 2021 Jul 20.
Endogenous cannabinoids (endocannabinoids [eCBs]) have been shown to have a multitude of functions including neurotransmission and immune modulatory effects. This study aimed to evaluate if stem cells of the apical papilla (SCAP) express the receptors and enzymes of the endocannabinoid system (ECS) and whether eCBs regulate their proliferation and mineralization potential.
Gene expression of the main components of the ECS and transient receptor potential vanilloid 1 (TRPV1) was evaluated in SCAP cultures. SCAP were treated with 2 concentrations of eCBs and/or capsazepine, a TRPV1 antagonist. SCAP viability was evaluated after 1, 4, and 7 days. Osteogenic differentiation was assessed after 14 days, and the gene expression of mineralization markers was assessed after 7 days.
The enzymes of ECS and TRPV1 but not the cannabinoid receptors (cannabinoid receptors 1 and 2) were expressed in SCAP. Anandamide, 2-arachidonoylglycerol, and N-arachidonoylphenolamine (AM-404) reduced SCAP viability in all experimental periods at the highest concentration compared with the group with no treatment. Anandamide and AM-404 did not inhibit SCAP differentiation potential, but 2-arachidonoylglycerol at the highest concentration did. SCAP treated with AM-404 presented a down-regulation in gene expression of alkaline phosphatase (ALP), dentin matrix protein 1 (DMP-1), and dentin sialophosphoprotein (DSPP) compared with the proliferation medium group but not with control group.
SCAP expressed the genes of the main components of ECS and TRPV1, and eCBs can affect SCAP viability, mineralization, and gene expression.
内源性大麻素（内源性大麻素[eCBs]）具有多种功能，包括神经递质传递和免疫调节作用。本研究旨在评估根尖乳头干细胞（SCAP）是否表达内源性大麻素系统（ECS）的受体和酶，以及内源性大麻素是否调节其增殖和矿化潜能。
在 SCAP 培养物中评估 ECS 和瞬时受体电位香草酸 1（TRPV1）的主要成分的基因表达。用 2 种浓度的内源性大麻素和/或辣椒素（TRPV1 拮抗剂）处理 SCAP。在第 1、4 和 7 天评估 SCAP 活力。在第 14 天评估成骨分化，在第 7 天评估矿化标志物的基因表达。
ECS 和 TRPV1 的酶，但不是大麻素受体（大麻素受体 1 和 2）在 SCAP 中表达。与无处理组相比，在所有实验期，最高浓度的大麻素类似物（anandamide）、2-花生四烯酰甘油和 N-花生四烯酰基苯甲胺（AM-404）均降低了 SCAP 的活力。anandamide 和 AM-404 不抑制 SCAP 分化潜能，但最高浓度的 2-花生四烯酰甘油抑制。与增殖培养基组相比，用 AM-404 处理的 SCAP 的碱性磷酸酶（ALP）、牙本质基质蛋白 1（DMP-1）和牙本质涎磷蛋白（DSPP）的基因表达下调，但与对照组相比无差异。
SCAP 表达 ECS 和 TRPV1 的主要成分的基因，内源性大麻素可影响 SCAP 的活力、矿化和基因表达。
