The results obtained by immunoblotting and quantitative real time

The results obtained by immunoblotting and quantitative real time PCR revealed that TNF enhanced the expression of CTGF in MH7A cells and this enhancement was neutralized by infliximab. The influence of TNF on CTGF pro duction for chondrocytes was also investigated using the OUMS 27. In contrast to synovial fibroblasts, newsletter subscribe CTGF produc tion was oppositely diminished by TNF stimulation and this inhibitory effect was restored by infliximab. These enhanced by the presence of CTGF with M CSF RANKL in comparison to the absence of CTGF in the culture. These data suggest CTGF promote osteoclastogenesis in the presence of M CSF RANKL and excessive CTGF is an impor tant factor of aberrant osteoclasts activation in RA pathogenesis.

CTGF activates focal adhesion kinase and extracellular signal regulated kinase 1 2 through integrin V 3 on the osteoclasts Although a specific receptor of CTGF has not been fully iden tified so far, several molecules have been reported as CTGF receptors. Chen and co workers reported that a neutralizing antibody against integrin Inhibitors,Modulators,Libraries V 3 significantly attenuated CTGF mediated ERK1 2 activation and cellular migration in human breast cancer cells, indicating that the integrin V 3 ERK1 2 signaling pathway is crucial in mediating CTGF function. Furthermore, Tan and co workers very recently found that CTGF stimulation increased the phosphorylation of FAK and ERK via integrin V 3 resulting in the Inhibitors,Modulators,Libraries migration and expres sion of matrix metalloproteinase Inhibitors,Modulators,Libraries 13 in human chondro sarcoma cells.

To date, several cell lines of evidence have shown that, among various integrins, osteoclasts express Inhibitors,Modulators,Libraries very high Inhibitors,Modulators,Libraries kinase inhibitor Wortmannin levels of integrin V 3 and it is now well accepted that this integrin is a central molecule for osteoclastic bone resorp tion. Therefore we considered that excessive CTGF pro duced by synovial fibroblasts in RA contribute to increased osteoclastic function through integrin V 3 signaling as well as other type of cells. To assess molecular actions of CTGF on osteoclasts, immunoprecipitation and immunoblotting analysis were performed. Figure 6 indicated that phosphorylated ERK1 2 was recruited by integrin V 3 upon CTGF stimula tion, and CTGF also induced FAK phosporylation. These data suggest that integrin V 3 is a recep tor of CTGF and CTGF could enhance osteoclastic function through activation of integrin V 3 signaling transduction pathways such as ERK1 2 and FAK phosphorylation. Discussion This study was conducted to investigate roles of CTGF for the possible pathogenesis of RA.

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