In vivo and In vitro Identification of Endocannabinoid Signaling in Periodontal Tissues and Their Potential Role in Local Pathophysiology

Abstract

The endocannabinoid system (ECS) with its binding receptors CB1 and CB2 impacts multiple pathophysiologies not only limited to neuronal psychoactivity. CB1 is assigned to cerebral neuron action, whereas CB2 is mainly expressed in different non-neuronal tissues and associated with immunosuppressive effects. Based on these tissue-selective CB receptor roles, it was the aim of this study to analyze potential expression in periodontal tissues under physiological conditions and inflammatory states. In vivo, CB receptor expression was investigated on human periodontal biopsies with or without bacterial inflammation and on rat maxillae with or without sterile inflammation. In vitro analyses were performed on human periodontal ligament (PDL) cells at rest or under mechanical strain via qRT-PCR, Western blot, and immunocytochemistry. P < 0.05 was set statistical significant. In vivo, CB1 expression was significantly higher in healthy PDL structures compared to CB2 (13.5% ± 1.3 of PDL tissues positively stained; 7.1% ± 0.9). Bacterial inflammation effected decrease in CB1 (9.7% ± 2.4), but increase in CB2 (14.7% ± 2.5). In contrast, sterile inflammation caused extensive CB1 (40% ± 1.9) and CB2 (41.7% ± 2.2) accumulations evenly distributed in the tooth surrounding PDL. In vitro, CB2 was ubiquitously expressed on gene and protein level. CB1 was constitutively expressed on transcriptional level (0.41% ± 0.09), even higher than CB2 (0.29% ± 0.06), but undetectable on protein level. Analyses further revealed expression changes of both receptors in mechanically loaded PDL cells. CB1 and CB2 are varyingly expressed in periodontal tissues, both adjusted by different entities of periodontal inflammation and by mechanical stress. This indicates potential ECS function as regulatory tool in controlling of periodontal pathophysiology.

Methanandamide diminish the Porphyromonas gingivalis lipopolysaccharide induced response in human periodontal ligament cells

“…Recently, the EC system is suggested as an important part of the neuroimmunoendocrine response in periodontal disease [49]. Our data, as well as data of previous studies [11,14,15,18,19], suggest that the EC system influences the inflammatory response in periodontitis. Emotional stress is associated with increased salivary levels of IL-6 and IL-8 [50].…”

“…An involvement of the EC system in periodontitis is also suggested by studies on cannabinoid receptor expression in periodontal tissue. An in vivo study on human periodontal biopsies shows that periodontitis is associated with a decreased expression of CB1 receptor and an increased expression of CB2 receptor [11]. Another study shows an increased expression of CB1 and CB2 receptors in inflamed gingival tissue [14].…”

“…Cannabinoid receptors belong to a transmembrane G-protein coupled receptor family. The primary endocannabinoid receptors cannabinoid receptor type 1 (CB1) and cannabinoid receptor type 2 (CB2) are expressed in various cells and tissues and particularly in dental tissues [11]. The EC system is thought to regulate several brain processes; however, actual studies suggest its involvement in the regulation of bone physiology and immune response [12,13].…”

CB1 enhanced the osteo/dentinogenic differentiation ability of periodontal ligament stem cells via p38 MAPK and JNK in an inflammatory environment

“…This study found that bacterial inflammation decreased CB1 expression in human periodontal ligament (PDL) cells. 19 However, it has been found that CB1 seems to be upregulated during gingival wound healing in rats. 30 To clarify the underlying role of CB1 in MSCs in mediating periodontal tissue regeneration, we explored the function and mechanism of CB1 in the osteo/dentinogenic differentiation of PDLSCs under inflammatory conditions.…”

A new target to ameliorate the damage of periodontal disease: The role of transient receptor potential vanilloid type‐1 in contrast to that of specific cannabinoid receptors in rats

“…In recent years, many studies have focused on the research of the ECS and its implication on immune and inflammatory diseases, including periodontal disease. [31][32][33] Most of these studies have approached this issue through cells cultures such as human gingival fibroblasts and ligament periodontal cells. 34 However, our research group reported anti-inflammatory effects on gingival tissue and osteoprotective effects on alveolar bone induced by both a CB2r and a CB1r agonist (HU308 and meth-AEA, respectively), in a model of LPS-induced periodontal disease in vivo.…”