tailieunhanh - Báo cáo y học: " Histone deacetylases — a new target for suppression of cartilage degradation"

Tuyển tập các báo cáo nghiên cứu về y học được đăng trên tạp chí y học General Psychiatry cung cấp cho các bạn kiến thức về ngành y đề tài: Histone deacetylases — a new target for suppression of cartilage degradation? | Available online http contents 7 4 155 Commentary Histone deacetylases - a new target for suppression of cartilage degradation John S Mort Shriners Hospital for Children and Department of Surgery McGill University Montreal Quebec Canada Corresponding author John S Mort jmort@ Published 16 June 2005 Arthritis Research Therapy 2005 7 155-156 DOI ar1781 This article is online at http content 7 4 155 2005 BioMed Central Ltd See related research by Young et al. http content 7 3 R503 Abstract Increased expression of metalloproteinases is a fundamental aspect of arthritis pathology 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. Proteolytic activity in articular cartilage is central to joint destruction in arthritis. Proteinase expression is well known to be modulated by cytokines intracellular signaling and transcription factor action but recent work by Young and colleagues 1 indicates that there is significantly more to this process than has been generally believed. The human genome is packed in a matrix of histones that shield it from transcription by RNA polymerase II. The basic unit of chromatin is the nucleosome core particle which consists of 147 bp of DNA wound times around a histone octamer composed of two copies each of four histone partners H2A H2B H3 and H4 .