Arg Gly Asp containing pep tides, RGD mimitics, and blocking find more antibodies to integrin V 3 were shown to inhibit bone resorption in vitro and in vivo, sug gesting that this integrin Inhibitors,Modulators,Libraries may play an important role in osteo clast function. It has been shown that CTGF could interact with integrin V 3 in other types of cells, however, it has not been shown to our knowledge that integrin V 3 on the osteoclasts interact with CTGF. Furthermore, blocking of the integrin V 3 signaling pathway has been shown to increase bone mineral density in women with postmenoposal osteoporosis. CTGF Integrin V 3 pathway is now receiving considerable attention as a therapeutic target in dis eases associated with Inhibitors,Modulators,Libraries increased bone resorption, such as RA.

Therefore, we insist that our findings are very important for the understanding of CTGF integrin V Inhibitors,Modulators,Libraries 3 contribution to disease progression in RA. Recently anti TNF blocking reagents are becoming more widely available in practical treatments for RA patients. Significant beneficial effects of infliximab on bone destruction have been reported even in RA patients without improvements of RA related clinical symptoms. Therefore, other mecha nisms besides the blocking of inflammatory reactions like CRP or ESR elevation appear to be associated with infliximab medi ated inhibition of articular damage in RA patients. The inhibi tion of CTGF production from synovial cells mediated by infliximab may play an important role in the blocking of bone destruction in RA patients. In this study, we also measured serum levels of TNF concomitant with CTGF, however, sig nificant correlation with serum levels of TNF and CTGF was not observed.

These data suggest that high levels of serum CTGF in active RA patients are not merely mediated by the production Inhibitors,Modulators,Libraries from synovial fibroblasts with TNF stimulation. Furthermore, although the production of CTGF has been reported to be induced by TGF in connective tis sues, no specific correlation Inhibitors,Modulators,Libraries was also observed between CTGF and TGF concentrations in the sera of RA patients. One possible explanation for these dissoci ations, high levels of serum CTGF production in active RA is mediated by other multiple stimulating factors or productive sites. In fact, IL 6, which is also the main proinflamatory cytokine related to RA pathogenesis, was reported as the stimulating factor of CTGF production.

Furthermore, vas cular endothelial cells, which are also affected by RA, are known as major productive sites of CTGF. These factors might be involved in mechanisms of considering the elevation of serum CTGF in active RA. In our study, TNF can induce CTGF production from syno vial cells. In contrast, TNF could oppositely inhibit the pro duction of CTGF from chondrocytes. It has been proposed that CTGF contributes to maintaining cartilage homeostasis by the autocrine system. CTGF also might promote the direct proliferation of osteoblasts.