Although a number of cell surface molecules have been nominated as candidates currently for its specific receptors, they have not been defined to date. CTGF is a bioactive cytokine, therefore, it is considered not to be derived from these destroyed cells. Furthermore, it has been shown that CTGF is associated with several biological Veliparib functions such as fibrosis, tumorgenesis, angiogenesis, and endochondral ossification, and it has been proposed that CTGF produced by chondrocytes might main tain a homeostasis of cartilage tissue by autocrine system. Articular tissue consists of not only chondrocytes but also various kinds of cells such as synovial fibroblasts or oste oclasts. Especially, fibroblasts of inflamed synovial tissue and osteoclasts are thought to be the main effecter cells for the development of bone destruction in RA.
However, precise Inhibitors,Modulators,Libraries functions of CTGF on these articular cells have not been elu cidated so far. Based on these findings, the contribution of CTGF for RA pathogenesis was investigated in the current study. Here, we report that aberrant CTGF production mediated by TNF can induce massive osteoclastogenesis Inhibitors,Modulators,Libraries and disturbance on home ostasis of cartilage resulting in bone and cartilage tissue dam age in RA. Furthermore, we report here that phosphorylated extracellular signal regulated kinase 1 2 was recruited by CTGF stimulation on activation of the signal transduction pathway associated with integrin V 3 and contributed to focal adhesion kinase activation on the osteoclasts. These data indicate that we found integrin V 3 as a CTGF receptor on the osteoclasts.
We insist that CTGF is a poten tially novel effecter molecule for RA pathogenesis and our data could help better understanding for elucidation of the protec tive mechanisms for bone destruction associated with the effi cacy of infliximab treatment. The Inhibitors,Modulators,Libraries blockade of the anti CTGF integrin V 3 pathway might become a new useful strategy for the treatment of RA. Materials and methods Patients and samples All patients with RA and systemic lupus erythematosus fulfilled the American College of Rheumatology criteria. All patients with Sj?grens syndrome also fulfilled the American European Consensus Criteria. Serum samples were obtained from 39 patients with RA, 11 patients with SLE, 4 patients with primary SS Inhibitors,Modulators,Libraries and 50 normal age and gender nearly matched healthy volunteers.
The syno vial tissue samples were obtained from two patients with RA and Inhibitors,Modulators,Libraries osteoarthropathy as disease controls during a surgi cal operation for knee joints arthropathy. The patients with RA were further categorized as an active RA group and inactive RA group depending on the elevated serum C reactive protein level. The active RA group includes the patients who had received inflix GW-572016 imab treatment. The precise clinical profiles of these patients had been described in a previous report and all these patients had shown disease amelioration by the infliximab treatment.
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