Abbreviations: BSA = bovine serum albumin; DD = differential display; DD-RT-PCR = differential display reverse transcriptase polymerase chain reaction; DMEM = Dulbecco's modified Eagle's medium; ECM = extracellullar matrix; ELISA = enzyme-linked immunosorbent assay; FACS = fluorescence-activated cell sorter; FBS = fetal bovine serum; FCS = fetal calf serum; H & E = hematoxylin and eosin; hTNF = human tumor necrosis factor; LF = lung fibroblast; MHC = major histocompatibility complex; MMP = matrix metalloproteinase; PBS = phosphate-buffered saline; PCR = polymerase chain reaction; RA = rheumatoid arthritis; RT = reverse transcriptase; SCID = severe combined immunodeficiency; SDS = sodium dodecyl sulfate; SF = synovial fibroblast; SPARC = secreted protein acidic and rich in cysteine; SSC = standard saline citrate; SSPE = standard sodium phosphate EDTA; SV40 = simian virus 40; TAg = large tumor antigen; TIMP = tissue inhibitor of metalloproteinases; TNF = tumor necrosis factor; tsTAg = temperature-sensitive large tumor antigen; VCAM = vascular cell adhesion molecule; wt = wild-type. Online ISSN 1478-6362). This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original URL.
Arthritis Research & Therapy Vol 5 No 3 Aidinis et al.
Research article
Functional analysis of an arthritogenic synovial fibroblast
AbstractIncreasing attention has been directed towards identifying non-T-cell mechanisms as potential therapeutic targets in rheumatoid arthritis. Synovial fibroblast (SF) activation, a hallmark of rheumatoid arthritis, results in inappropriate production of chemokines and matrix components, which in turn lead to bone and cartilage destruction. We have demonstrated that SFs have an autonomous pathogenic role in the development of the disease, by showing that they have the capacity to migrate throughout the body and cause pathology specifically to the joints. In order to decipher the pathogenic mechanisms that govern SF activation and pathogenic potential, we used the two most prominent methods of differential gene expression analysis, differential display and DNA microarrays, in a search for deregulated cellular pathways in the arthritogenic SF. Functional clustering of differentially expressed genes, validated by dedicated in vitro functional assays, implicated a number of cellular pathways in SF activation. Among them, diminished adhesion to the extracellullar matrix was shown to correlate with increased proliferation and migration to this matrix. Our findings support an aggressive role for the SF in the development of the disease and reinforce the perspective of a transformed-like character of the SF.
An oral isotonic drink postdischarge can have a prophylactic effect on patients with a newly formed ileostomy, preventing readmission for fluid and electrolyte abnormalities. See Video Abstract at http://links.lww.com/DCR/A603.
Epidemiological studies have shown that low plasma levels of High Density Lipoprotein Cholesterol (HDL-C) are associated with an increased risk for myocardial infarction. These studies suggested that by increasing HDL-C levels one could reduce cardiovascular risk. However, emerging evidence from studies in animals and humans indicate that high levels of HDL-C are not sufficient to confer atheroprotection but that the functionality of the HDL particles is equally important. The picture is complicated further by the finding that HDL functionality is compromised in patients with chronic inflammatory diseases such as Coronary Artery Disease (CAD), diabetes and rheumatoid arthritis. Despite these obstacles, HDL raising is still a promising strategy for the reduction of CAD risk. Low HDL-C can be caused by inactivating mutations in apoA-I, ATP Binding Cassette Transporter A1 (ABCA1) or Lecithin-Cholesterol Acyl Transferase (LCAT) which affect HDL biogenesis and maturation whereas high HDL-C can be caused by mutations in Cholesteryl Ester Transfer Protein (CETP) or Scavenger receptor Class B Type I (SR-BI). Recent studies suggest that heterogeneity in HDL levels in the population is polygenic in origin. One approach to raise plasma HDL-C is to increase the rate of HDL biosynthesis by capitalizing on the mechanisms that control the transcription of genes that play key roles in HDL biogenesis. We review some of the genetic and non-genetic factors that affect plasma HDL levels and functions and discuss the mechanisms that regulate HDL metabolism at the level of gene transcription in the liver focusing on apoA-I, ABCA1 and apoM.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.