TY - JOUR A1 - Gómez Bahamonde, Rodolfo AU - Conde Aranda, Javier AU - Scotece, Morena AU - López López, Verónica AU - Lago Paz, Francisca AU - Gómez-Reino Carnota, Juan Jesús AU - Gualillo ., Oreste T1 - Endogenous cannabinoid anandamide impairs cell growth and induces apoptosis in chondrocytes Y1 - 2014 SN - 0736-0266 UR - http://hdl.handle.net/20.500.11940/4629 AB - Endocannabinoids has been described to be involved in articular degenerative disease by modulating nociception and immune system. However, the role of the endocannabinoid anandamide on chondrocyte cell viability is still unclear. Therefore, we decided to study anandamide's effects on chondrocytes viability and to evaluate its interactions with the catabolic factor TNF (tumor necrosis factor). Chondrocyte vitality was evaluated by MTT assay. We investigated LDH release, chromatin condensation, cleavage of focal adhesion kinase (FAK), and caspases-3, 8, and 9 activation. c-MYC mRNA levels were determined by RT-PCR. We studied by Western blot the activation patterns of AKT, AMPK, ERK, p38, and JNK kinases. Finally, we evaluate the effect of anandamide in TNF-induced caspase-3 cleavage. Anandamide decreased chondrocyte vitality independently of its receptors. It induced AMPK activation without LDH release. Anandamide induced chromatin condensation, activation of caspase-3, 8, and 9, and FAK cleavage. Surprisingly, despite anandamide inhibited cell proliferation, it increased c-MYC expression. Moreover anandamide inhibited AKT activation, whilst it induced a sustained activation of ERK, JNK, and p38. Finally, anandamide synergized with TNF-alpha in the cleavage of caspase-3. In conclusion, our findings suggest that anandamide, alone or in combination with TNF-alpha, may be a potential destructive agent in cartilage. KW - AMP-Activated Protein Kinases KW - Animals KW - Apoptosis KW - Arachidonic Acids KW - Cannabinoids KW - Caspases KW - Cell Line KW - Cell Proliferation KW - Chondrocytes KW - Chromatin/drug effects KW - Endocannabinoids KW - MAP Kinase Signaling System KW - Mice KW - Models, Animal KW - Polyunsaturated Alkamides KW - Proto-Oncogene Proteins c-akt KW - Signal Transduction/drug effects KW - Tumor Necrosis Factor-alpha KW - Tnf| LA - eng ER -