In vivo and In vitro Identification of Endocannabinoid Signaling in Periodontal Tissues and Their Potential Role in Local Pathophysiology
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.
KeywordsCannabinoid receptors CB1 CB2 Inflammation Neurotransmitter Periodontal ligament cells Periodontal pathophysiology
The authors would like to thank H. Schrage from the Institute of Molecular Psychiatry as much as I. Bay-Müller K. Reifenrath and J. Marciniak from the Department of Orthodontics, University of Bonn as much as S. Daecke from the Department of Oncology and Hematology, University of Bonn, for technical support.
Compliance with Ethical Standards
Conflict of interest
All authors disclose any potential conflict of interest.
- Napimoga MH, Benatti BB, Lima FO, Alves PM, Campos AC, Pena-Dos-Santos DR, Severino FP, Cunha FQ, Guimarães FS (2009) Cannabidiol decreases bone resorption by inhibiting RANK/RANKL expression and pro-inflammatory cytokines during experimental periodontitis in rats. Int Immunopharmacol 9:216–222CrossRefPubMedGoogle Scholar
- Onaivi ES, Ishiguro H, Gong JP, Patel S, Perchuk A, Meozzi PA, Myers L, Mora Z, Tagliaferro P, Gardner E, Brusco A, Akinshola BE, Liu QR, Hope B, Iwasaki S, Arinami T, Teasenfitz L, Uhl GR (2006) Discovery of the presence and functional expression of cannabinoid CB2 receptors in brain. Ann N Y Acad Sci 1074:514–536CrossRefPubMedGoogle Scholar