Evaluation of Cannabinoids on the Odonto/osteogenesis in Human Dental Pulp Cells In Vitro

Introduction: Cannabinoids possess anti-inflammatory, analgesic and osteogenic effects in different cell types and tissues. The null hypothesis is delta-9-tetrahydrocannabinol (THC) might induce dental tissue repair and regeneration. The aim of this study was to investigate the effect of THC on human dental pulp cell (HDPC) viability and biomineralization, as well as the molecular mechanism of THC-induced odonto/osteogenic differentiation of HDPCs.

Methods: The toxicity of THC on HDPCs was determined by MTT assay. The odonto/osteogenic differentiation marker genes of HDPCs were assessed by RT-PCR with or without THC treatment. HDPCs biomineralization was examined by collagen synthesis and calcium nodule deposition. The molecular mechanism of THC on HDPCs was investigated by examining the MAPK signaling pathway via blocking CB1 or CB2 receptors.

Results: We found that THC had no inhibition of HDPC vitality in the testing concentration (0-100 μM). THC showed biphasic effects on HDPCs proliferation. At low dose (<5 μM), THC considerably increased HDPC cell division. HDPC proliferation reduced with higher THC concentrations (>5 μM). The expression of odonto/osteogenic marker genes were upregulated in the presence of cannabinoids. These were confirmed by increased collagen synthesis and mineralized calcium nodule formation in cannabinoids group. The effect of THC-induced odonto/osteogenesis occured via MAPK signaling.

Conclusion: THC was biocompatible to HDPCs by promoting their mitogenic division in a biphasic pattern depending on the concentration. THC induced HDPCs odonto/osteogenic differentiation through activation of MAPK mediated by CB1 and CB2 receptors. Cannabinoids may play an important role in HDPCs regeneration process, and potentially be used as a pulp-capping agent.