Cannabidiol Rescues TNF-α-Inhibited Proliferation, Migration, and Osteogenic/Odontogenic Differentiation of Dental Pulp Stem Cells

Strategies to promote dental pulp stem cells (DPSCs) functions including proliferation, migration, pro-angiogenic effects, and odontogenic/osteogenic differentiation are in urgent need to restore pulpitis-damaged dentin/pulp regeneration and DPSCs-based bone tissue engineering applications. Cannabidiol (CBD), an active component of Cannabis sativa has shown anti-inflammation, chemotactic, anti-microbial, and tissue regenerative potentials. Based on these facts, this study aimed to analyze the effect of CBD on DPSCs proliferation, migration, and osteogenic/odontogenic differentiation in basal and inflammatory conditions. Highly pure DPSCs with characteristics of mesenchymal stem cells (MSCs) were successfully isolated, as indicated by the results of flowcytometry and multi-lineage (osteogenic, adipogenic, and chondrogenic) differentiation potentials. Among the concentration tested (0.1-12.5 mu M), CBD (2.5 mu M) showed the highest anabolic effect on the proliferation and osteogenic/odontogenic differentiation of DPSCs. Pro-angiogenic growth factor VEGF mRNA expression was robustly higher in CBD-treated DPSCs. CBD also prompted the migration of DPSCs and CBD receptor CB1 and CB2 expression in DPSCs. TNF-alpha inhibited the viability, migration, and osteogenic/odontogenic differentiation of DPSCs and CBD reversed these effects. CBD alleviated the TNF-alpha-upregulated expression of pro-inflammatory cytokines TNF-alpha, interleukin (IL)-1 beta, and IL-6 in DPSCs. In conclusion, our results indicate the possible application of CBD on DPSCs-based dentin/pulp and bone regeneration.