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: Slit3 inhibits Robo3-induced invasion of synovial fibroblasts in rheumatoid arthritis. | Denk et al. Arthritis Research Therapy 2010 12 R45 http content 12 2 R45 RESEARCH ARTICLE Open Access Slit3 inhibits Robo3-induced invasion of synovial fibroblasts in rheumatoid arthritis Alexandra E Denk1 Simone Kaufmann1 Klaus Stark2 Jorg Schedel3 Torsten Lowin3 Thomas Schubert1 Anja K Bosserhoff1 Abstract Introduction The repellent factor family of Slit molecules has been described to have repulsive function in the developing nervous system on growing axons expressing the Robo receptors. However until today no data are available on whether these repellent factors are involved in the regulation of synovial fibroblast SF activity in rheumatoid arthritis RA . Methods mRNA expression in primary synovial fibroblasts was quantified by quantitative reverse transcription PCR and protein expression was measured by fluorescence activated cell sorting FACS analysis. Different functional assays were performed with rheumatoid arthritis synovial fibroblasts RASF proliferation migration and a novel in-vitro cartilage destruction assay. Results First we found increased expression of Robo3 expression in RASF compared to normal SF. Interestingly analysis of data from a recently published genome-wide association study suggests a contribution of ROBO3 gene polymorphisms to susceptibility of RA. Functional assays performed with RASF revealed induction of migration and cartilage destruction by Robo3 and increased matrix metalloproteinase MMP 1 and MMP3 expression. Treatment of RASF in early passages with Slit3 led to inhibition of migration whereas RASF in later passages having reduced Robo3 expression in cell culture were not inhibited by Slit3 treatment. Here reduction of Robo3 expression from passage 3 to 10 might reflect an important step in losing repulsive activity of Slit3. Conclusions Taken together our data showed that deregulation of the Robo3 receptor in synovial fibroblasts in RA correlates with aggressiveness of the fibroblasts. Slit3 reduces the .