Evaluation of Cannabinoids on the Odonto/Osteogenesis in Human Dental Pulp Cells In Vitro
Xia Qi1, Chunyan Liu2, Guohua Li3
1Graduate Periodontics, School of Dentistry, University of Detroit Mercy, Detroit, Michigan; Department of Periodontics, School and Hospital of Stomatology, Hebei Medical University and Hebei Key Laboratory of Stomatology, Shijiazhuang, Hebei, China.
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 3-(4,5-dimethylthiazolyl-2-yl)-2,5-diphenyltetrazolium bromide assay. The odonto/osteogenic differentiation marker genes of HDPCs were assessed by real-time polymerase chain reaction with or without THC treatment. HDPC biomineralization was examined by collagen synthesis and calcium nodule deposition. The molecular mechanism of THC on HDPCs was investigated by examining the mitogen-activated protein kinase (MAPK) signaling pathway via blocking cannabinoid receptor type 1 or 2 receptors.
Results:
We found that THC had no inhibition of HDPC vitality in the testing concentration (0-100 μmol/L). THC showed biphasic effects on HDPC proliferation. At a low dose (<5 μmol/L), THC considerably increased HDPC cell division. HDPC proliferation reduced with higher THC concentrations (>5 μmol/L). The expression of odonto/osteogenic marker genes were up-regulated in the presence of cannabinoids. These were confirmed by increased collagen synthesis and mineralized calcium nodule formation in the cannabinoid group. The effect of THC-induced odonto/osteogenesis occurred via MAPK signaling.
Conclusions:
THC was biocompatible to HDPCs by promoting their mitogenic division in a biphasic pattern depending on the concentration. THC induced HDPC odonto/osteogenic differentiation through the activation of MAPK mediated by CB1 and CB2 receptors. Cannabinoids may play an important role in the HDPC regeneration process and potentially be used as a pulp-capping agent.
