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Suppression of titanium particle-induced TNF-alpha expression and apoptosis in human U937 macrophages by siRNA silencing.
|Title||Suppression of titanium particle-induced TNF-alpha expression and apoptosis in human U937 macrophages by siRNA silencing.|
|Publication Type||Journal Article|
|Year of Publication||2013|
|Authors||Sun K, Li Y, Lu Z, Zhang L, Gao Z, Jin Q|
|Journal||The International journal of artificial organs|
|Date Published||2013 Jul|
Aseptic loosening of joint prosthetics is one of the most frequent reasons for the failure of total joint replacement surgeries. A major cause of the aseptic loosening is osteolysis caused by a periprosthetic inflammatory response to wear particles released from implanted prosthetics. Tumor necrosis factor (TNF)-α is thought to play a dominant role in wear-induced inflammation. It was shown previously by our group, as well as by other researchers, that macrophages produce abundant TNF-α when exposed to particulate titanium (Ti), which is widely used as a biomaterial in arthroplastic surgery. In the present study, we have tested the feasibility of using siRNA as a therapeutic intervention against wear-induced TNF-α production. Our data show that transfection of U937 macrophage cells with TNF-α siRNA inhibits Ti particle-induced expression of TNF-α mRNA and protein by >65%. Moreover, U937 cells transfected with TNF-α siRNA were significantly more resistant to Ti particle-induced apoptosis (>60%, p<0.05) and caspase-3 activation (>50%, p<0.05) compared with normal U937 cells. Collectively, our data show that siRNA can be an effective way to inhibit Ti particle-induced TNF-α expression and the activation of downstream pathways such as apoptosis in macrophages. These data provide a foundation for future studies to investigate the use of siRNA targeting inflammatory cytokines as a therapeutic modality for the treatment of aseptic loosening of prosthetic materials used in arthroplastic surgery.
|Alternate Journal||Int J Artif Organs|