Involvement of the endocannabinoid system in periodontal healing

• Published in: Biochemical and biophysical research communications Vol. 394; no. 4; pp. 928 - 933
• Main Authors: Kozono, Sayaka, Matsuyama, Takashi, Biwasa, Kamal Krishna, Kawahara, Ko-ichi, Nakajima, Yumiko, Yoshimoto, Takehiko, Yonamine, Yutaka, Kadomatsu, Hideshi, Tancharoen, Salunya, Hashiguchi, Teruto, Noguchi, Kazuyuki, Maruyama, Ikuro
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 16.04.2010
• Subjects: 60 APPLIED LIFE SCIENCES; Animals; Arachidonic Acids - metabolism; Arachidonic Acids - pharmacology; Cannabinoid Receptor Modulators - metabolism; Cannabinoid Receptor Modulators - pharmacology; Cannabinoid receptors; Cell Proliferation; Endocannabinoids; FIBROBLASTS; Fibroblasts - drug effects; Fibroblasts - metabolism; Fibroblasts - physiology; Gingival Crevicular Fluid - metabolism; Gingival fibroblasts; Glycerides - metabolism; Glycerides - pharmacology; GRANULATION; GTP-ASES; HEALING; Humans; IN VITRO; Indoles - pharmacology; LIPIDS; MACROPHAGES; Mitogen-activated protein kinases; ORGANS; p38 Mitogen-Activated Protein Kinases - metabolism; Periodontium - injuries; Periodontium - metabolism; Phosphatidylinositol 3-Kinases - metabolism; PHOSPHORYLATION; PHOSPHOTRANSFERASES; Piperidines - pharmacology; Polyunsaturated Alkamides - metabolism; Polyunsaturated Alkamides - pharmacology; Proliferation; Pyrazoles - pharmacology; RATS; Receptor, Cannabinoid, CB1 - antagonists & inhibitors; Receptor, Cannabinoid, CB1 - metabolism; Receptor, Cannabinoid, CB2 - antagonists & inhibitors; Receptor, Cannabinoid, CB2 - metabolism; RECEPTORS; Wound Healing; WOUNDS; Wound healing; Proliferation; Endocannabinoids; Gingival fibroblasts; Cannabinoid receptors; Mitogen-activated protein kinases
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2010.03.080

Endocannabinoids including anandamide (AEA) and 2-arachidonoylglycerol (2-AG) are important lipid mediators for immunosuppressive effects and for appropriate homeostasis via their G-protein-coupled cannabinoid (CB) receptors in mammalian organs and tissues, and may be involved in wound healing in some organs. The physiological roles of endocannabinoids in periodontal healing remain unknown. We observed upregulation of the expression of CB1/CB2 receptors localized on fibroblasts and macrophage-like cells in granulation tissue during wound healing in a wound-healing model in rats, as well as an increase in AEA levels in gingival crevicular fluid after periodontal surgery in human patients with periodontitis. In-vitro, the proliferation of human gingival fibroblasts (HGFs) by AEA was significantly attenuated by AM251 and AM630, which are selective antagonists of CB1 and CB2, respectively. CP55940 (CB1/CB2 agonist) induced phosphorylation of the extracellular-regulated kinases (ERK) 1/2, p38 mitogen-activated protein kinase (p38MAPK), and Akt in HGFs. Wound closure by CP55940 in an in-vitro scratch assay was significantly suppressed by inhibitors of MAP kinase kinase (MEK), p38MAPK, and phosphoinositol 3-kinase (PI3-K). These findings suggest that endocannabinoid system may have an important role in periodontal healing.