title: The carbon monoxide-releasing molecule tricarbonyldichlororuthenium(II) dimer protects human osteoarthritic chondrocytes and cartilage from the catabolic actions of interleukin-1beta.
abstract: We have investigated the effects of a carbon monoxide-releasing molecule, tricarbonyldichlororuthenium(II) dimer (CORM-2), on catabolic processes in human osteoarthritis (OA) cartilage and chondrocytes activated with interleukin-1beta. In these cells, proinflammatory cytokines induce the synthesis of matrix metalloproteinases (MMPs) and aggrecanases, including members of a disintegrin and metalloproteinase with thrombospondin domain (ADAMTS) family, which may contribute to cartilage loss. CORM-2 down-regulated MMP-1, MMP-3, MMP-10, MMP-13, and ADAMTS-5 in OA chondrocytes, and it inhibited cartilage degradation. These effects were accompanied by increased aggrecan synthesis and collagen II expression in chondrocytes. Our results also indicate that the inhibition of extracellular signal-regulated kinase 1/2 and p38 activation by CORM-2 may contribute to the maintenance of extracellular matrix homeostasis. These observations suggest that CORM-2 could exert chondroprotective effects due to the inhibition of catabolic activities and the enhancement of aggrecan synthesis.
authors.affiliation: Department of Pharmacology, Faculty of Pharmacy, University of Valencia, Av. Vicent Andres Estelles s/n, 46100 Burjasot, Valencia, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Megías
authors.forename: María Isabel
authors.initials: MI
authors.lastname: Guillén
authors.forename: Antonio
authors.initials: A
authors.lastname: Bru
authors.forename: Francisco
authors.initials: F
authors.lastname: Gomar
authors.forename: María José
authors.initials: MJ
authors.lastname: Alcaraz
mesh_terms: D000368:Aged; D053674:Aggrecans / Q000096:biosynthesis; D002248:Carbon Monoxide; D002356:Cartilage / Q000187:drug effects / Q000473:pathology*; D019902:Chondrocytes / Q000473:pathology*; D024043:Collagen Type II / Q000096:biosynthesis; D015536:Down-Regulation / Q000187:drug effects; D005260:Female; D006801:Humans; D053583:Interleukin-1beta / Q000494:pharmacology*; D008297:Male; D020782:Matrix Metalloproteinases / Q000235:genetics; D009942:Organometallic Compounds / Q000494:pharmacology* / Q000627:therapeutic use; D010003:Osteoarthritis / Q000188:drug therapy* / Q000473:pathology / Q000517:prevention & control; D020011:Protective Agents / Q000494:pharmacology
chemical_list: D053674:Aggrecans; D024043:Collagen Type II; D053583:Interleukin-1beta; D009942:Organometallic Compounds; D020011:Protective Agents; C447082:tricarbonyldichlororuthenium (II) dimer; D002248:Carbon Monoxide; D020782:Matrix Metalloproteinases