Department of Restorative Dentistry and Endodontology, Kagoshima University, Graduate School of Medical and Dental Sciences, Kagoshima, Japan.
J Endod. 2012 Jun;38(6):786-90. doi: 10.1016/j.joen.2012.02.025. Epub 2012 Apr 11.
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).
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.
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.
We demonstrated for the first time that AEA induced MMP-2 production via CB1 and TRPV1 in HPC.
花生四烯酸乙醇胺（N-花生四烯酰乙醇胺[AEA]）是主要的内源性大麻素之一。内源性大麻素参与多种生理和病理功能，不仅能引起痛觉，还能促进再生和炎症。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 诱导的影响。
我们通过 Western blot 检测了 AEA 诱导的 MMP-2 产生和 HPC 中 AEA 受体（大麻素[CB]受体-1、CB2 和瞬时受体电位香草醛-1[TRPV1]）的表达。通过酶联免疫吸附试验测定上清液中 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。
AEA 显著诱导 HPC 中 MMP-2 的产生。HPC 表达 3 种类型的 AEA 受体（CB1、CB2 和 TRPV1）。CB1 或 TRPV1 拮抗剂以及针对 CB1 或 TRPV1 的小干扰 RNA 阻断了 AEA 诱导的 MMP-2 产生。此外，c-Jun N-末端激酶抑制剂也减少了 MMP-2 的产生。
我们首次证明 AEA 通过 HPC 中的 CB1 和 TRPV1 诱导 MMP-2 产生。
