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.
To read this article in full you will need to make a payment
Purchase one-time access:Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
One-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:Subscribe to Journal of Endodontics
Already a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
- Matrix metalloproteinases in health and disease: regulation by melatonin.J Pineal Res. 2011; 50: 8-20
- Matrix metalloproteinase-8 (MMP-8) in pulpal and periapical inflammation and periapical root canal exudates.Int Endod J. 2002; 35: 897-904
- The upregulation of matrix metalloproteinase-9 in inflamed human dental pulps.J Endod. 2005; 31: 860-862
- Tissue levels of matrix metalloproteinases in pulps and periapical lesions.J Endod. 2002; 28: 313-315
- Matrix metalloproteinase expression in teeth with apical periodontitis is differentially modulated by the modality of root canal treatment.J Endod. 2010; 36: 231-237
- The role of the endocannabinoid system in atherosclerosis.J Neuroendocrinol. 2008; 20: S53-S57
- Peripheral effects of the endocannabinoid system in energy homeostasis: adipose tissue, liver and skeletal muscle.Rev Endocr Metab Disord. 2011; 12: 153-162
- Allergen challenge increases anandamide in bronchoalveolar fluid of patients with allergic asthma.Clin Pharmacol Ther. 2011; 90: 388-391
- Cannabinoid receptor CB1-immunoreactive nerve fibres in painful and non-painful human tooth pulp.J Clin Neurosci. 2010; 17: 1476-1479
- Capsaicin-evoked iCGRP release from human dental pulp: a novel system for the study of peripheral neuropeptide secretion in normal healthy tissue.Pain. 2009; 144: 253-261
- Expression and characterization of vanilloid receptor subtype 1 in human dental pulp cell cultures.J Endod. 2005; 31: 652-658
- Antiangiogenic activity of the endocannabinoid anandamide: correlation to its tumor-suppressor efficacy.J Cell Physiol. 2007; 211: 495-503
- Genetic and pharmacologic inactivation of cannabinoid CB1 receptor inhibits angiogenesis.Blood. 2011; 117: 5541-5550
- Regulation of interleukin-6 expression in human dental pulp cell cultures stimulated with Prevotella intermedia lipopolysaccharide.J Endod. 2001; 27: 273-277
- Roxithromycin inhibits tumor necrosis factor-α-induced matrix metalloproteinase-1 expression through regulating mitogen-activated protein kinase phosphorylation and Ets-1 expression.J Periodontal Res. 2007; 42: 53-61
- Runt-related gene 2 is involved in the inhibition of matrix metalloproteinase-13 expression by roxithromycin in human gingival epithelial cell cultures.J Periodontal Res. 2009; 44: 283-288
- Neuroprotective agents: cannabinoids.Clin Immunol. 2012; 142: 57-67
- The pharmacology of cannabinoid receptors and their ligands: an overview.Int J Obes. 2006; 30: S13-S18
- Segmental regulation of sodium and water excretion by TRPV1 activation in the kidney.J Cardiovasc Pharmacol. 2008; 51: 437-442
- TRPV1 in migraine pathophysiology.Trends Mol Med. 2010; 16: 153-159
- The endocannabinoid system and pain.CNS Neurol Disord Drug Targets. 2009; 8: 403-421
- Effect of a synthetic cannabinoid agonist on the proliferation and invasion of gastric cancer cells.J Cell Biochem. 2010; 110: 321-332
- Regression of fibrosis after chronic stimulation of cannabinoid CB2 receptor in cirrhotic rats.J Pharmacol Exp Ther. 2008; 324: 475-483
- α-mangostin suppresses phorbol 12-myristate 13-acetate-induced MMP-2/MMP-9 expression via αvβ3 integrin/FAK/ERK and NF-κB signaling pathway in human lung adenocarcinoma A549 cells.Cell Biochem Biophys. 2010; 58: 31-44
- Benzyl isothiocyanate (BITC) inhibits migration and invasion of human colon cancer HT29 cells by inhibiting matrix metalloproteinase-2/-9 and urokinase plasminogen (uPA) through PKC and MAPK signaling pathway.J Agric Food Chem. 2010; 58: 2935-2942
- Anethole exerts antimetastatic activity via inhibition of matrix metalloproteinase 2/9 and AKT/mitogen-activated kinase/nuclear factor kappa B signaling pathways.Biol Pharm Bull. 2011; 34: 41-46
- Angiotensin II induces MMP 2 activity via FAK/JNK pathway in human endothelial cells.Biochem Biophys Res Commun. 2009; 380: 769-774
- Antimetastatic potential of fisetin involves inactivation of the PI3K/Akt and JNK signaling pathways with downregulation of MMP-2/9 expressions in prostate cancer PC-3 cells.Mol Cell Biochem. 2010; 333: 169-180
- Quantification of endocannabinoids in biological systems by chromatography and mass spectrometry: a comprehensive review from an analytical and biological perspective.Biochim Biophys Acta. 2011; 1811: 706-723
Published online: April 13, 2012
Supported by Grants-in-Aid for Scientific Research (#22592125 and #22592124) from the Ministry of Education, Science, and Culture of Japan.
© 2012 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.