Molecular signatures and new candidates to target the pathogenesis of rheumatoid arthritis

Abstract

A, Neidel J, Lehrach H, Thiesen HJ, Ruiz P, Bläß S. Molecular signatures and new candidates to target the pathogenesis of rheumatoid arthritis.

Human Synovial Lubricin Expresses Sialyl Lewis x Determinant and Has L-selectin Ligand Activity

“…PMN) may adhere to cartilage, leading to destruction of cartilage. It has been reported that low expression levels of lubricin were associated with a strong synovial stromal activation (22), characterized by the infiltration of T cells and macrophages, and was associated with a higher destructive potential and a worse prognosis (63). Prg4 knock-out mice exhibited a degenerative phenotype, including synovial hyperplasia and abnormal cartilage surface (64).…”

“…Loss-of-function mutations in the PRG4 gene causes the camptodactyly-arthropathy-coxa vara-pericarditis syndrome in humans, a syndrome of precocious joint failure associated with non-inflammatory synovial hyperplasia and subintimal fibrosis of the joint capsule (3). Lubricin is found heterogeneously expressed in the synovium of rheumatoid arthritis (RA) and osteoarthritis (OA), implying a role in the pathogenesis of these diseases (21,22). RA patients varied with respect to lubricin expression, where the patients with low levels of lubricin had more aggressive joint disease (22).…”

“…Lubricin is found heterogeneously expressed in the synovium of rheumatoid arthritis (RA) and osteoarthritis (OA), implying a role in the pathogenesis of these diseases (21,22). RA patients varied with respect to lubricin expression, where the patients with low levels of lubricin had more aggressive joint disease (22). A relationship between the pathogenesis of OA and down-regulation of lubricin has been suggested in several animal models (23)(24)(25)(26).…”

Comparative genome-wide gene expression analysis of rheumatoid arthritis and osteoarthritis

“…We used microarray dataset GSE1919 from GEO (www.ncbi.nlm.nih.gov/geo/) (Ungethuem et al, 2010). In this genome-wide dataset, the two disease conditions of RA and OA were investigated and the data were compared to those of normal donors (NDs).…”

Systems Approach to Rheumatoid Arthritis

“…Accordingly, to understand fundamental mechanisms of RA pathogenesis, it is essential to identify and analyze RA-perturbed networks in the RA synovium. Several studies have identified RA-associated genes (RAGs) and their associated cellular processes [4,5,6]. For example, Hurber et al [4] analyzed mRNA expression profiles in the synovial tissues of RA patients and normal controls.…”