RRC ID 61533
Author Gómez R, Conde J, Scotece M, López V, Lago F, Gómez Reino JJ, Gualillo O.
Title Endogenous cannabinoid anandamide impairs cell growth and induces apoptosis in chondrocytes.
Journal J Orthop Res
Abstract 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-α in the cleavage of caspase-3. In conclusion, our findings suggest that anandamide, alone or in combination with TNF-α, may be a potential destructive agent in cartilage.
Volume 32(9)
Pages 1137-46
Published 2014-9
DOI 10.1002/jor.22660
PMID 24902823
MeSH AMP-Activated Protein Kinases / drug effects AMP-Activated Protein Kinases / metabolism Animals Apoptosis / drug effects* Arachidonic Acids / pharmacology* Cannabinoids / pharmacology* Caspases / drug effects Caspases / metabolism Cell Line Cell Proliferation / drug effects* Chondrocytes / drug effects Chondrocytes / pathology* Chromatin / drug effects Endocannabinoids / pharmacology* MAP Kinase Signaling System / drug effects MAP Kinase Signaling System / physiology Mice Models, Animal Polyunsaturated Alkamides / pharmacology* Proto-Oncogene Proteins c-akt / drug effects Proto-Oncogene Proteins c-akt / metabolism Signal Transduction / drug effects Tumor Necrosis Factor-alpha / pharmacology
Human and Animal Cells ATDC5(RCB0565)