Differential Expression of Cannabinoid Receptors in Oral Tissues

Objectives: In recent years many US states have decriminalized cannabis possession and legalized its medicinal use. This raises concerns about the oral health implications of cannabis consumption. Cannabis activates the cellular signaling cascade to initiate its biologic effects by binding to two G protein coupled receptors, CB1 and CB2. The aim of this study is to investigate the distributions of cannabinoid receptors in oral tissue, to provide clues for further exploration of the impacts of cannabis on oral health.
Methods: Normal human gingival tissues are collected during distal wedge or esthetic crown lengthening surgeries. Mouse oral tissues are harvested from 12-week old C57BL6 mice. The locations of CB1 and CB2 receptors in oral tissue are determined by immunohistochemistry. Human gingival cell line (HGF1), osteoblast cell line (MG63), and primary cultured periodontal ligament cells are utilized to characterize the regulation of cannabinoid (THC) on the cellular markers and signaling transduction pathways by Western blot, real time PCR, and immunostainings etc. CB1 and CB2 antagonists, such as AM251 and AM630 are used to test their specific effects.
Results: Although both CB1 and CB2 are expressed in the periodontal tissues in human and in mouse, they show different expression levels and distinct distribution patterns. Both CB1 and CB2 are highly expressed in the perivascular cells. CB2 expresses abundantly in junctional epithelial cells and osteoblasts, while CB1 is rich in subepithelial connective tissues. Compared to osteoblasts, gingival fibroblasts express more CB1 but less CB2. Cannabinoid (THC) activates multiple cellular signaling pathways, including MAPK, NFkB, and Stat etc. They exhibit different receptor-dependent properties.
Conclusions: The differential expression of cannabinoid receptors in periodontal tissues and different biologic behaviors under the stimulation of cannabinoid may play import roles in regulation cell and tissue functions in oral tissue.