Endogenous cannabinoid anandamide impairs cell growth and induces apoptosis in chondrocytes
| Autor: | Gómez Bahamonde, Rodolfo, Conde Aranda, Javier, Scotece, Morena, López López, Verónica, Lago Paz, Francisca, Gómez-Reino Carnota, Juan Jesús, Gualillo ., Oreste |
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| Rok vydání: | 2014 |
| Předmět: |
Tnf
Cannabinoids MAP Kinase Signaling System Polyunsaturated Alkamides Tumor Necrosis Factor-alpha Apoptosis Arachidonic Acids AMP-Activated Protein Kinases Cell Line Mice Chondrocytes Chromatin/drug effects Caspases Signal Transduction/drug effects Models Animal Animals Proto-Oncogene Proteins c-akt Cell Proliferation Endocannabinoids |
| Zdroj: | RUNA. Repositorio da Consellería de Sanidade e Sergas Servizo Galego de Saúde (SERGAS) |
| Popis: | 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. Instituto de Salud Carlos III Xunta de Galicia (SERGAS) RETICS Programme, RD08/0075 (RIER) via Instituto de Salud Carlos III (ISCIII) “FPU” programme of the Spanish Ministry of Education Instituto de Salud Carlos III (ISCIII)/ “Sara Borrell Programme” |
| Databáze: | OpenAIRE |
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