Rheumatoid arthritis: Still a chronic disease
Department of Clinical Immunology and Rheumatology, Immunogenomics and Inflammation Research Unit, University of Lyon, Edouard Herriot Hospital, Lyon 69437, France. Electronic address: .The Lancet (Impact Factor: 45.22). 01/2013; 381(9870). DOI: 10.1016/S0140-6736(12)62192-8
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ABSTRACT: The knowledge of rheumatoid arthritis (RA) pathology is rapidly advancing and becoming more and more complex, and a simple fact is that the major organ targeted by RA pathogenic factors is the synovium. It is well known that fibroblast-like synovial (FLS) cell is the major cell-type for constructing synovium. Following stimulation by pro-inflammatory cytokines, FLS cells are phenotypically changed to have the capability to proliferate abnormally. Recently we demonstrated that α-actinin-1 (ACTN1) gene is significantly increased in synovial tissues obtained from RA, as compared to osteoarthritis (OA). We therefore reviewed the literature about α-actinins (ACTNs) and we now propose that ACTN1 may function as a "terminal effector" of intracellular signalings initiated by tumor necrosis factor-α (TNF-α) and interleukin-1 (IL-1) in RA. Future research on ACTN1 may help to improve the current therapeutic and diagnostic strategies of RA.Discovery medicine 02/2014; 17(92):75-80. · 3.63 Impact Factor
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ABSTRACT: To investigate the potential regulation of sphingosine kinase 1 (SPHK1) on the migration, invasion, and matrix metalloproteinase (MMP) expression in human rheumatoid arthritis fibroblast-like synoviocytes (RA-FLS). RA-FLS were transfected control siRNA or SPHK1 siRNA. The migration and invasion of unmanipulated control, control siRNA or SPHK1 siRNA- transfected RA-FLS in vitro were measured by the transwell system. The relative levels of SPHK1, PI3K, and AKT as well as AKT phosphorylation in RA-FLS were determined by Western blot. The levels of MMP-2/9 secreted by RA-FLS were detected by ELISA. Knockdown of SPHK1 significantly inhibited the spontaneous migration and invasion of RA-FLS, accompanied by significantly reduced levels of PI3K expression and AKT phosphorylation. Similarly, treatment with LY294002, an inhibitor of the PI3K/AKT pathway, inhibited the migration and invasion of RA-FLS. Knockdown of SPHK1 and treatment with the inhibitor synergistically inhibited the migration and invasion of RA-FLS, by further reducing the levels of PI3K expression and AKT phosphorylation. In addition, knockdown of SPHK1 or treatment with LY294002 inhibited the secretion of MMP-2 and MMP-9, and both synergistically reduced the production of MMP-2 and MMP-9 in RA-FLS in vitro. Knockdown of SPHK1 expression inhibits the PI3K/AKT activation, MMP-2 and MMP-9 expression, and human RA-FLS migration and invasion in vitro. Potentially, SPHK1 may be a novel therapeutic target for RA.Molecular Biology Reports 05/2014; 41(8). DOI:10.1007/s11033-014-3382-4 · 2.02 Impact Factor
- Arthritis Research & Therapy 06/2014; 16(3):113. DOI:10.1186/ar4592 · 3.75 Impact Factor
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