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INFLAMMATION, IMMUNOPHARMACOLOGY, AND ASTHMA

The Carbon Monoxide-Releasing Molecule Tricarbonyldichlororuthenium(II) Dimer Protects Human Osteoarthritic Chondrocytes and Cartilage from the Catabolic Actions of Interleukin-1β

Department of Pharmacology, Faculty of Pharmacy, University of Valencia, Burjasot, Valencia, Spain (J.M., M.I.G., M.J.A.); Department of Chemistry, Biochemistry, and Molecular Biology, Cardenal Herrera-CEU University, Moncada, Valencia, Spain (M.I.G.); Department of Orthopaedic Surgery and Traumatology, General Hospital, Valencia, Spain (A.B.); and Department of Surgery, Faculty of Medicine, University of Valencia, Spain (F.G.)

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.

Address correspondence to: Dr. María José Alcaraz, Department of Pharmacology, Faculty of Pharmacy, University of Valencia, Av. Vicent Andres Estelles s/n, 46100 Burjasot, Valencia, Spain. E-mail: maria.j.alcaraz{at}uv.es

This article has been cited by other articles:

				M. I. Guillen, J. Megias, V. Clerigues, F. Gomar, and M. J. Alcaraz The CO-releasing molecule CORM-2 is a novel regulator of the inflammatory process in osteoarthritic chondrocytes Rheumatology, September 1, 2008; 47(9): 1323 - 1328. [Abstract] [Full Text] [PDF]