arachidonyl-2-chloroethylamide and Osteoarthritis

Senescence of chondrocytes and cartilage degeneration induced by the proinflammatory cytokine interleukin-1β is associated with the pathogenesis of osteoarthritis. The cannabinoid receptor 1 has been involved in the pathological development of various diseases. Here, we evaluated whether activation of cannabinoid receptor 1 using its selective agonist arachidonyl-2-chloroethylamide had an influence on cellular senescence induced by interleukin-1βin human chondrocytes. Our findings demonstrate that agonist arachidonyl-2-chloroethylamidedecreased senescence-associated β-galactosidase activity and cell cycle arrest in the G0/G1 phase induced by interleukin-1β. Importantly, our results display interleukin-1βtreatment significantly increased the expressions of senescence genes (caveolin-1, PAI-1 and p21), which were prevented by agonist arachidonyl-2-chloroethylamide treatment. However, it was noticed that these functions of agonist arachidonyl-2-chloroethylamide were abolished by the cannabinoid receptor 1 selective antagonist AM251, suggesting the involvement of cannabinoid receptor 1. Also, our results indicate that agonist arachidonyl-2-chloroethylamide enhanced the expression of sirt1. These findings suggest that activation of cannabinoid receptor 1 by agonist arachidonyl-2-chloroethylamide might have a protective effect against pro-inflammatory cytokines such as interleukin-1β-induced chondrocytes senescence in osteoarthritis patients. Impact statement Senescence of chondrocytes and cartilage degeneration induced by the proinflammatory cytokine interleukin-1β (IL-1β) are associated with the pathogenesis of osteoarthritis (OA). Here we found that: (a) the CB1 agonist ACEA abolished IL-1β-induced senescence and cell arrest in chondrocytes; (b) the CB1 agonist ACEA also abolished IL-1β-induced expression of caveolin-1, PAI-1, and p21;

Topics: Arachidonic Acids; beta-Galactosidase; Caveolin 1; Cells, Cultured; Cellular Senescence; Chondrocytes; Cyclin-Dependent Kinase Inhibitor p21; Enzyme Activation; Female; G1 Phase Cell Cycle Checkpoints; Humans; Interleukin-1beta; Male; Middle Aged; Osteoarthritis; Piperidines; Plasminogen Activator Inhibitor 1; Pyrazoles; Receptor, Cannabinoid, CB1; Sirtuin 1