Histone deacetylases--a new target for suppression of cartilage degradation?
Increased expression of metalloproteinases is a fundamental aspect of arthritispathology and its control is a major therapeutic objective. In cartilage cultured in the presence of the cytokines interleukin-1 and oncostatin M, chondrocytes produce enhanced levels of metalloproteinases of the ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) and MMP (matrix metalloproteinase) families, resulting in the degradation of aggrecan and collagen. The histone deacetylase inhibitors trichostatin A and butyrate were shown to drastically reduce expression of these enzymes relatively selectively, with concomitant inhibition of breakdown of matrix components. This family of enzymes is therefore a promising target for therapeutic intervention.
Mort
John S
JS
Shriners Hospital for Children, Department of Surgery, McGill University, Montreal, Quebec, Canada. jmort@shriners.mcgill.ca
D000818:Animals; D002356:Cartilage / Q000187:drug effects / Q000201:enzymology; D002357:Cartilage Diseases / Q000188:drug therapy* / Q000201:enzymology; D016503:Drug Delivery Systems / Q000379:methods*; D004791:Enzyme Inhibitors / Q000008:administration & dosage*; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases / Q000378:metabolism; D006801:Humans
D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases