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

Xia Qi; Chunyan Liu; Guohua Li; Dalia Al-Alfe; Susan Paurazas; Mazin Askar; Dongru Yang; Zheng Zhou

doi:10.1016/j.joen.2020.12.005

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

J Endod. 2021 Mar;47(3):444-450. doi: 10.1016/j.joen.2020.12.005. Epub 2021 Jan 20.

Authors

Xia Qi¹, Chunyan Liu², Guohua Li³, Dalia Al-Alfe⁴, Susan Paurazas⁴, Mazin Askar⁴, Dongru Yang⁵, Zheng Zhou⁶

Affiliations

¹ Graduate 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.
² Graduate Periodontics, School of Dentistry, University of Detroit Mercy, Detroit, Michigan; Department of Orthodontics, School and Hospital of Stomatology, Hebei Medical University and Hebei Key Laboratory of Stomatology, Shijiazhuang, Hebei, China.
³ Graduate Periodontics, School of Dentistry, University of Detroit Mercy, Detroit, Michigan.
⁴ Graduate Endodontics, School of Dentistry, University of Detroit Mercy, Detroit, Michigan.
⁵ Department of Periodontics, School and Hospital of Stomatology, Hebei Medical University and Hebei Key Laboratory of Stomatology, Shijiazhuang, Hebei, China; Graduate Periodontics, School of Dentistry, University of Detroit Mercy, Detroit, Michigan. Electronic address: yangdr@hebmu.edu.cn.
⁶ Graduate Periodontics, School of Dentistry, University of Detroit Mercy, Detroit, Michigan. Electronic address: zhouzh1@udmercy.edu.

PMID: 33352148
DOI: 10.1016/j.joen.2020.12.005

Abstract

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.

Keywords: Cannabinoid; delta-9-tetrahydrocannabinol; human dental pulp cell; odontogenesis.

MeSH terms

Cannabinoids* / toxicity
Cell Differentiation
Cell Proliferation
Cells, Cultured
Dental Pulp
Humans
Osteogenesis*

Substances

Cannabinoids