Anandamide Induces Matrix Metalloproteinase-2 Production through Cannabinoid-1 Receptor and Transient Receptor Potential Vanilloid-1 in Human Dental Pulp Cells in Culture
Anandamide Induces Matrix Metalloproteinase-2 Production through Cannabinoid-1 Receptor and Transient Receptor Potential Vanilloid-1 in Human Dental Pulp Cells in Culture
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DOI：
10.1016/j.joen.2012.02.025
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发表时间：
2012-06-01
影响因子：
4.2
通讯作者：
Torii, Mitsuo
中科院分区：
文献类型：
--
作者：
Miyashita, Keiko;Oyama, Tohru;Torii, Mitsuo
Anandamide（N-arachidonoyethanolamine [AEA]）是一种主要的内源性大麻素。内源性大麻素参与各种生理和病理功能，不仅诱导伤害感受，还诱导再生和炎症。最近描述了内源性大麻素系统在外周器官中的作用。本研究旨在探讨AEA对人牙髓细胞（HPC）基质金属蛋白酶（MMP）-2的诱导作用。研究方法：我们通过Western blot检测了AEA诱导的MMP-2产生和AEA受体（大麻素[CB]受体-1，CB 2和瞬时受体电位香草素-1 [TRPV 1]）在HPC中的表达。采用酶联免疫吸附法测定培养上清中MMP-2的浓度。然后，我们研究了AEA受体和丝裂原活化蛋白激酶在AEA诱导的HPC中MMP-2产生中的作用。结果：AEA能显著诱导HPC中MMP-2的产生。HPC表达所有3种类型的AEA受体（CB1、CB2和TRPV 1）。AEA诱导的MMP-2的产生被CB1或TRPV1拮抗剂和CB1或TRPV1的小干扰RNA阻断。此外，c-Jun N-末端激酶抑制剂也减少MMP-2的产生。结论：我们首次证明AEA通过CB1和TRPV1诱导HPC中MMP-2的产生。（J Endod 2012; 38：786 - 790）
Introduction: Anandamide (N-arachidonoylethanolamine [AEA]) is one of the main endocannabinoids. Endocannabinoids are implicated in various physiological and pathologic functions, inducing not only nociception but also regeneration and inflammation. The role of the endocannabinoid system in peripheral organs was recently described. The aim of this study was to investigate the effect of AEA on matrix metalloproteinase (MMP)-2 induction in human dental pulp cells (HPC). Methods: We examined AEA-induced MMP-2 production and the expression of AEA receptors (cannabinoid [CB] receptor-1, CB2, and transient receptor potential vanilloid-1 [TRPV1]) in HPC by Western blot. MMP-2 concentrations in supernatants were determined by enzyme-linked immunosorbent assay. We then investigated the role of the AEA receptors and mitogen-activated protein kinase in AEA-induced MMP-2 production in HPC. Results: AEA significantly induced MMP-2 production in HPC. HPC expressed all 3 types of AEA receptor (CB1, CB2, and TRPV1). AEA-induced MMP-2 production was blocked by CB1 or TRPV1 antagonists and by small interfering RNA for CB1 or TRPV1. Furthermore, c-Jun N-terminal kinase inhibitor also reduced MMP-2 production. Conclusions: We demonstrated for the first time that AEA induced MMP-2 production via CB1 and TRPV1 in HPC. (J Endod 2012;38:786-790)