title: Carvedilol suppresses cartilage matrix destruction.
abstract: 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)-1β 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-1β 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-1β 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-1β increased phosphorylation of IKK-α/β and degradation of IκB-α in SW1353 chondrocytes, which were suppressed by pretreatment with Carvedilol. Administration of Carvedilol inhibited IL-1β-induced translocation of NF-κB p65 from cytosol to nucleus manner. Notably, a luciferase reporter assay showed that IL-1β severely increased NF-κB luciferase activity, which was markedly suppressed by Carvedilol treatment. Our results suggest that Carvedilol might be a potential therapeutic agent for chondro-protective therapy.
authors.affiliation: Department of Biomedical Engineering, Faculty of Electronic Information and Electrical Engineering, Dalian University of Technology, Dalian, Liaoning, PR China; Department of Orthopaedics, Affiliated Zhongshan Hospital of Dalian University, Dalian, Liaoning, PR China.
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Orthopaedics, Affiliated Zhongshan Hospital of Dalian University, Dalian, Liaoning, PR China.
authors.forename: Baoyi
authors.initials: B
authors.lastname: Liu
authors.affiliation: Department of Orthopaedics, Affiliated Zhongshan Hospital of Dalian University, Dalian, Liaoning, PR China.
authors.forename: Benjie
authors.initials: B
authors.lastname: Wang
authors.affiliation: Department of Orthopaedics, Affiliated Zhongshan Hospital of Dalian University, Dalian, Liaoning, PR China.
authors.forename: Yupeng
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Orthopaedics, Affiliated Zhongshan Hospital of Dalian University, Dalian, Liaoning, PR China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Orthopaedics, Affiliated Zhongshan Hospital of Dalian University, Dalian, Liaoning, PR China.
authors.forename: Fengde
authors.initials: F
authors.lastname: Tian
authors.affiliation: Department of Orthopaedics, Affiliated Zhongshan Hospital of Dalian University, Dalian, Liaoning, PR China.
authors.forename: Borui
authors.initials: B
authors.lastname: Li
authors.affiliation: Department of Orthopaedics, Affiliated Zhongshan Hospital of Dalian University, Dalian, Liaoning, PR China. Electronic address: dwzhao0908@163.com.
authors.forename: Dewei
authors.initials: D
authors.lastname: Zhao
mesh_terms: D002227:Carbazoles / Q000008:administration & dosage*; D002358:Cartilage, Articular / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D000077261:Carvedilol; D002460:Cell Line; D019902:Chondrocytes / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D004305:Dose-Response Relationship, Drug; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D016326:Extracellular Matrix Proteins / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D011412:Propanolamines / Q000008:administration & dosage*
chemical_list: D002227:Carbazoles; D016326:Extracellular Matrix Proteins; D011412:Propanolamines; D000077261:Carvedilol
keywords: Carvedilol; Collagen type Ⅱ; MMP-1; NF-κB; Osteoarthritis (OA)