Involvement of the endocannabinoid system in periodontal healing
Involvement of the endocannabinoid system in periodontal healing
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DOI：
10.1016/j.bbrc.2010.03.080
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发表时间：
2010-04-16
影响因子：
3.1
通讯作者：
Maruyama, Ikuro
中科院分区：
文献类型：
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作者：
Kozono, Sayaka;Matsuyama, Takashi;Maruyama, Ikuro
内源性大麻素包括大麻素（anandamide，AEA）和2-花生四烯酸甘油（2-arachidonoylglycerol，2-AG）是重要的脂质介质，通过它们的G-蛋白偶联大麻素（CB）受体在哺乳动物器官和组织中发挥免疫抑制作用和适当的体内平衡，并且可能参与一些器官中的伤口愈合。内源性大麻素在牙周愈合中的生理作用仍然未知。我们观察到在大鼠伤口愈合模型中，伤口愈合过程中肉芽组织中成纤维细胞和巨噬细胞样细胞上的CB 1/CB 2受体表达上调，以及牙周炎患者牙周手术后龈沟液中AEA水平增加。在体外实验中，CB 1和CB 2的选择性拮抗剂AM 251和AM 630可显著抑制AEA诱导的人牙龈成纤维细胞（HGF）增殖。CP 55940（CB 1/CB 2激动剂）诱导HGF中细胞外调节激酶（ERK）1/2、p38丝裂原活化蛋白激酶（p38 MAPK）和Akt的磷酸化。在体外划痕试验中，MAP激酶激酶（MEK）、p38 MAPK和磷酸肌醇3-激酶（PI 3-K）抑制剂显著抑制了CP 55940的伤口闭合。这些结果表明，内源性大麻素系统可能在牙周愈合中发挥重要作用。(C)2010年爱思唯尔公司All rights reserved.
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. (C) 2010 Elsevier Inc. All rights reserved.