There is mounting evidence indicating that the synovial fibroblast is a direct effector of tissue injury and matrix remodeling in inflammatory synovitis. Through the elaboration of effector signals including cytokines and chemokines, mesenchymal cells stimulate or suppress inflammation via autocrine and paracrine mechanisms. Synovial fibroblasts are the principal cells mediating joint destructi...

Rheumatoid arthritis (RA) is a progressive autoimmune disease affecting the joints. In this study, we investigated the role of the pro-angiogenic factor leptin in regulating reactive oxygen species (ROS) to promote cell migration and angiogenesis in RA. We showed that leptin triggered RA fibroblast-like synoviocyte (FLS) migration by increased ROS expression. Additionally, leptin enhanced human...

We are developing retroviral-mediated gene transfer to human fibroblast-like synovial cells (FLS) as one approach to characterizing genetic pathways involved in synoviocyte pathophysiology. Prior work has suggested that FLS are relatively refractory to infection by Moloney murine leukemia virus based vectors. To determine if viral titer influenced the transduction efficiency of FLS, we optimize...

OBJECTIVE Osteopontin (OPN) is a proinflammatory cytokine that plays an important role in the pathogenesis of rheumatoid arthritis (RA). OPN can be cleaved by thrombin, resulting in OPN-R and exposing the cryptic C-terminal alpha4beta1 and alpha9beta1 integrin-binding motif (SVVYGLR). Thrombin-activatable carboxypeptidase B (CPB), also called thrombin-activatable fibrinolysis inhibitor, removes...

Synoviocyte adhesion, migration, and proliferation are essential in the growth of pannus and the subsequent invasion of cartilage in inflammatory arthritis. These cellular functions are regulated by the extracellular matrix.' In vitro studies of synoviocytes have previously demonstrated that they display abnormal phenotypic properties, including a transformation-like morphology manifested by ce...

Background: TNF-mediated fibroblast-like synoviocyte (FLS) activation is important for inflammation and joint destruction in rheumatoid arthritis (RA). The role of TNF-receptor 1 (TNFR1) FLS has thoroughly been characterized. functions TNFR2 are, however, largely unknown. Objectives: To investigate the contribution to FLS. Methods: RA-FLS were transfected with TNFR2-targeting siRNA pools transc...

The PTPN11 gene, encoding the tyrosine phosphatase SHP-2, is overexpressed in rheumatoid arthritis (RA) fibroblast-like synoviocytes (FLS) compared with osteoarthritis (OA) FLS and promotes RA FLS invasiveness. Here, we explored the molecular basis for PTPN11 overexpression in RA FLS and the role of SHP-2 in RA pathogenesis. Using computational methods, we identified a putative enhancer in PTPN...