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.
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- Mesenchymal stem cell-mediated functional tooth regeneration in swine.PLoS One. 2006; 1: e79
- Survival of the apical papilla and its resident stem cells in a case of advanced pulpal necrosis and apical periodontitis.J Endod. 2017; 43: 561-567
- The hidden treasure in apical papilla: the potential role in pulp/dentin regeneration and bioroot engineering.J Endod. 2008; 34: 645-651
- Prognosis of luxated non-vital maxillary incisors treated with calcium hydroxide and filled with gutta-percha. A retrospective clinical study.Endod Dent Traumatol. 1992; 8: 45-55
- Microbial modulation of stem cells and future directions in regenerative endodontics.J Endod. 2017; 43: S95-S101
- Prostaglandin E2 affects interleukin 6 and monocyte chemoattractant protein 1/CCL2 production by cultured stem cells of apical papilla.J Endod. 2020; 46: 413-418
- Anti-inflammatory effect of the endocannabinoid anandamide in experimental periodontitis and stress in the rat.Neuroimmunomodulation. 2012; 19: 293-303
- Cannabinoid receptor signaling in progenitor/stem cell proliferation and differentiation.Prog Lipid Res. 2013; 52: 633-650
- Paracetamol: new vistas of an Old Drug.CNS Drug Rev. 2006; 12: 250-275
- Characterization of the endocannabinoid system in mouse embryonic stem cells.Stem Cells Dev. 2011; 20: 139-147
- The cytochrome P450 inhibitor, ketoconazole, inhibits oxidized linoleic acid metabolite-mediated peripheral inflammatory pain.Mol Pain. 2012; 8: 73
- The functions of TRPA1 and TRPV1: moving away from sensory nerves.Br J Pharmacol. 2012; 166: 510-521
- Cannabinoids stimulate fibroblastic colony formation by bone marrow cells indirectly via CB2 receptors.Calcif Tissue Int. 2007; 80: 50-59
- TRPV1-mediated calcium signal couples with cannabinoid receptors and sodium-calcium exchangers in rat odontoblasts.Cell Calcium. 2012; 52: 124-136
- Anandamide induces matrix metalloproteinase-2 production through cannabinoid-1 receptor and transient receptor potential vanilloid-1 in human dental pulp cells in culture.J Endod. 2012; 38: 786-790
- A new target to ameliorate the damage of periodontal disease: the role of transient receptor potential vanilloid type-1 in contrast to that of specific cannabinoid receptors in rats.J Periodontol. 2019; 90: 1325-1335
- Differential roles of TLR2 and TLR4 in recognition of gram-negative and gram-positive bacterial cell wall components.Immunity. 1999; 11: 443-451
- The I kappa B/NF-kappa B system: a key determinant of mucosalinflammation and protection.Am J Physiol Cell Physiol. 2000; 278: C451-C462
- Prostaglandin E2 acts via bone marrow macrophages to block PTH-stimulated osteoblast differentiation in vitro.Bone. 2013; 56: 31-41
- The cannabinoid receptor type 1 is essential for mesenchymal stem cell survival and differentiation: implications for bone health.Stem Cells Int. 2013; 2013: 796715
- Effect of irrigants on the survival of human stem cells of the apical papilla in a platelet-rich plasma scaffold in human root tips.J Endod. 2011; 37: 1109-1115
- The role of SDF-1 and CXCR4 on odontoblastic differentiation in human dental pulp cells.Int Endod J. 2014; 47: 534-541
- Inflammation and Toll-like receptor ligation differentially affect the osteogenic potential of human mesenchymal stromal cells depending on their tissue origin.Tissue Eng Part A. 2012; 18: 1410-1418
- Expression of cannabinoid type 1 receptors in human odontoblast cells.J Endod. 2017; 43: 283-288
- Expression and distribution of three transient receptor potential vanilloid (TRPV) channel proteins in human odontoblast-like cells.J Mol Histol. 2017; 48: 367-377
- Anadamide induces apoptosis in human cells via vanilloid receptors.J Biol Chem. 2000; 41: 31938-31945
- TRPV1 mediates cellular uptake of anandamide and thus promotes endothelial cell proliferation and network-formation.Biol Open. 2014; 3: 1164-1172
- The effects of the endocannabinoids anandamide and 2-arachidonoylglycerol on human osteoblast proliferation and differentiation.PLoS One. 2015; 10: e0136546
- International union of basic and clinical pharmacology. LXXIX. Cannabinoid receptors and their ligands: beyond CB₁ and CB₂.Pharmacol Rev. 2010; 62: 588-631
- Receptors and channels targeted by synthetic cannabinoid receptor agonists and antagonists.Curr Med Chem. 2010; 17: 1360-1381
Published online: July 19, 2021
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