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 -