Inhibitory Effects Of Adenovirus-mediated Sirna Targeting BMPR-IA On Titanium Particle-induced Osteoclastogenesis And Osteolysis

Objective:To detect the role of BMPR-IA in regulating the differentiation and maturation of osteoclasts induced by wear debris.To investigate the effect of BMPR-IA silencing and overexpression on the marker gene of osteoclast and understand the mechanism of BMPs and BMP receptors in osteolysis.Methods:Vivo experimentA mouse calvarial osteolysis model was established.The formation and maturation of osteoclasts were detected by micro-CT,TRAP staining,immunohistochemistry and bone resorption pit assay.To observe whether siBMPR-IA inhibits the maturation of osteoclasts induced by wear debris in vivo,and inhibits the osteolysis effectively.Vitro experimentThe siBMPR-IA was transfected into primary osteoclasts extracted from BALB /C mice.To detect the activation of the osteoclast differentiation signaling pathway induced by titanium particles through staining with TRAP(tartrate-resistant acid phosphatase).To observe the expression of the osteoclast marker gene in RANKL / RANK signaling pathway(RANK,RANKL,Ctsk,OPG,NFATc1)with Real-Time PCR.Results:1.The siRNA targeting BMPR-IA can effectively inhibits osteolysis caused by osteoclast differentiation and maturation in a mouse calvarial osteolysis model.2.The siBMPR-IA mediating on osteoclast precursor cells and osteoblasts,inhibits osteoclastogenesis by regulating the expression of osteoclast marker gene(Ctsk?RANKL?OPG?NFATc1?RANKL).Conclusion:The study confirmed that the BMPR-IA / MAPK signal axis plays an important role in the differentiation and maturation of osteoclasts.The siBMPR-IA can effectively inhibit the osteolysis in a calvarial osteolysis model.BMPR-IA / MAPK signal axis can mediate the differentiation and maturation of osteoclasts directly and indirectly.It may become a new target for the treatment of aseptic loosening of prosthesis caused by osteolysis in the future.