Carvedilol suppresses cartilage matrix destruction

Collagen type II (col II) and aggrecan, the main components of the extracellular matrix (ECM) in human joint cartilage, have been reported to be reduced by chronic production of inflammatory cytokine interleukin (IL)-beta in arthritic joints. Carvedilol, a licensed medicine, has been used for treatment of hypertension, congestive heart failure and coronary disease in clinics. In this study, we investigated the effects of Carvedilol on the expression of col II and aggrecan. Our results demonstrate that treatment with Carvedilol didn't change the expression of aggrecan or col II at mRNA levels in SW1353 chondrocytes. However, the expression of aggrecan and Col II at protein levels were significantly reduced by IL-beta treatment, which were reversed by Carvedilol in a dose dependent manner, suggesting the inhibitory effects of Carvedilol on the expression of aggrecan and Col II are at post-translational modification levels. In addition, it was shown that IL-beta treatment highly induced MMP-1 and MMP-13 expression in SW1353 chondrocytes at both gene and protein expression levels, which were restored by Carvedilol in a dose dependent manner. Mechanistically, exposure to IL-beta increased phosphorylation of IKK-alpha/beta and degradation of IKB-a in SW1353 chondrocytes, which were suppressed by pretreatment with Carvedilol. Administration of Carvedilol inhibited IL-beta-induced translocation of NF-KB p65 from cytosol to nucleus manner. Notably, a luciferase reporter assay showed that IL-beta severely increased NE KB luciferase activity, which was markedly suppressed by Carvedilol treatment. Our results suggest that Carvedilol might be a potential therapeutic agent for chondro-protective therapy. (C) 2016 Published by Elsevier Inc.