BMP-2and Titanium Particles Synergistically Activated Osteoclast Formation

Objective: To study the effect of BMP-2on wears debris-inducedosteoclast formation in the presence of RANKL.Method and Results: In this study, We find that BMP-2synergize withtitanium particles to enhance osteoclast formation in the presence of RNAKL invitro and at low concentration, BMP-2has optimal effect to stimulate the sizeand number of multinuclear osteoclasts, expression of osteoclast gene, andresorption area. Our data also show that BMP-2increased in phosphorylatedSMAD levels as the increased expression of c-Fos throughout the early stages ofosteoclastogenesis. BMP-2and titanium particles stimulate expression of p-JNK,p-P38, p-IkB and p50compare with titanium group. To further confirmed ourresults, we construct an adenoviral vector carrying TNF-siRNA(Ad-TNF-siRNA), and carrying both BMP-2gene and TNF-α-siRNA gene(Ad-BMP-2-TNF-siRNA). Both the two adenoviral vectors dramaticallysuppressed the expression of TNF-α, but only the Ad-TNF-siRNA treatmentsignificantly inhibited osteoclastogenesis. We demonstrate that overexpressingBMP-2and meanwhile, suppressing TNF-α expression byAd-BMP-2-TNF-siRNA can also increase the size and number of titaniumparticles-induced multinuclear osteoclasts, expression of osteoclast gene, andresorption area. There were no different between Ti particles-induced andAd-BMP2-TNFsiRNA-induced osteoclast formation.Conclusion: We have demonstrated that BMP-2increased differentiation of titanium particles-induced osteoclast differentiation of RAW264.7cells in thepresence of suboptimal level of RANKL by activating p-JNK p-P38and p-IkBsignaling pathways.