RT Journal Article
SR Electronic
T1 The Carbon Monoxide-Releasing Molecule Tricarbonyldichlororuthenium(II) Dimer Protects Human Osteoarthritic Chondrocytes and Cartilage from the Catabolic Actions of Interleukin-1β
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 56
OP 61
DO 10.1124/jpet.107.134650
VO 325
IS 1
A1 Javier Megías
A1 María Isabel Guillén
A1 Antonio Bru
A1 Francisco Gomar
A1 María José Alcaraz
YR 2008
UL http://jpet.aspetjournals.org/content/325/1/56.abstract
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