Activation of the cannabinoid receptor 1 by ACEA suppresses senescence in human primary chondrocytes through sirt1 activation. Issue 5 (March 2018)

• Record Type: Journal Article
• Authors: Zhang, Dawei; Zhang, Gang; Li, Zongyu; Li, Bingsheng
• Is Part Of: Experimental biology and medicine. Volume 243:Issue 5(2018)
• Page Start: 437
• Page End: 443
• Publication Date: 2018-03
• Subjects: Osteoarthritis -- cannabinoid receptor 1 -- senescence -- Sirt1; Physiology -- Periodicals; Biology, Experimental -- Periodicals; Medicine, Experimental -- Periodicals; 610.72
• DOI: 10.1177/1535370218757950
• Languages: English
• ISSNs: 1535-3702

Abstract

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; (c) ACEA regulated the expression of sirt1; (d) the inhibitory effects of ACEA on senescence were mediated by sirt1.