PT  - JOURNAL ARTICLE
AU  - Javier Megías
AU  - María Isabel Guillén
AU  - Antonio Bru
AU  - Francisco Gomar
AU  - María José Alcaraz
TI  - The Carbon Monoxide-Releasing Molecule Tricarbonyldichlororuthenium(II) Dimer Protects Human Osteoarthritic Chondrocytes and Cartilage from the Catabolic Actions of Interleukin-1β
AID  - 10.1124/jpet.107.134650
DP  - 2008 Apr 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 56--61
VI  - 325
IP  - 1
4099  - http://jpet.aspetjournals.org/content/325/1/56.short
4100  - http://jpet.aspetjournals.org/content/325/1/56.full
SO  - J Pharmacol Exp Ther2008 Apr 01; 325
AB  - 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-1β. 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. The American Society for Pharmacology and Experimental Therapeutics