tailieunhanh - Báo cáo y học: "New insights into the pathogenesis of glucocorticoid-induced avascular necrosis: microarray analysis of gene expression in a rat model"

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: New insights into the pathogenesis of glucocorticoid-induced avascular necrosis: microarray analysis of gene expression in a rat model. | Kerachian et al. Arthritis Research Therapy 2010 12 R124 http content 12 3 R124 RESEARCH ARTICLE Open Access New insights into the pathogenesis of glucocorticoid-induced avascular necrosis microarray analysis of gene expression in a rat model Mohammad Amin Kerachian1 Denis Cournoyer1 2 3 Edward J Harvey4 Terry Y Chow3 Louis R Begin5 Ayoub Nahal6 and Chantal Seguin 2 3 Abstract Introduction Avascular necrosis of the femoral head ANFH occurs variably after exposure to corticosteroids. Microvascular thrombosis is a common pathological finding. Since systemic thrombophilia is only weakly linked with ANFH we propose that microvascular vessel pathology may be more related to local endothelial dysfunction and femoral head apoptosis. Corticosteroid effects on the endothelium and resultant apoptosis have been reported. We hypothesize that corticosteroids contribute to a differential gene expression in the femoral head in rats with early ANFH. Methods Besides bone marrow necrosis which is a common sign in ANFH and reported in the early stages we include the presence of apoptosis in this study as a criterion for diagnosing early disease. Forty Wistar Kyoto WKY rats were randomized to either a corticosteroid-treated group or an age-matched control group for six months. After sacrifice the femoral heads were examined for ANFH. Total mRNA was extracted from femoral heads. Affymetrix exon array Santa Clara CA USA was performed on 15 selected RNA samples. Validation methods included RT-PCR and immunohistochemistry IHC . Results Although rat exon array demonstrated a significant upregulation of 51 genes corticosteroid ANFH VS control alpha-2-macroglobulin A2M gene was particularly over-expressed. Results were validated by RT-PCR and IHC. Importantly A2M is known to share vascular osteogenic and cartilage functions relevant for ANFH. Conclusions The findings suggest that corticosteroid-induced ANFH in rats might be mediated by A2M. Investigation of A2M as a .