Abstract:Objective To investigate the role of extracellular signal regulated kinase (ERK) signaling pathway in inflammatory osteolysis induced by titanium particles in mice. Methods After preparing the back air sac and implanting the donor mouse skull slices successfully,forty-five female SPF BALB/c mice were randomly divided into three groups (n=15,each):blank control group (PBS was injected into air sac,normal saline was injected intraperitoneally),model group (titanium particle suspension was injected into air sac,normal saline was injected intraperitoneally) and titanium particle+ERK inhibitor group (titanium particle suspension was injected into air sac and titanium particle suspension was injected intraperitoneally) (intraperitoneal injection of ERK inhibitor PD98059).Two weeks later,the mice were killed under anesthesia and the implanted skull and air sac wall tissue were removed.The morphology of implanted skull and the formation of osteoclasts were observed and evaluated.The expression of nitric oxide (NO),tumor necrosis factor (TNF)-α,interleukin (IL)-1β,IL-6,NF-κB receptor activator factor (RANK) and RANK ligand (RANKL) were detected.Results Compared with the blank control group,in the model group,the bone fragments implanted with air sac were seriously damaged,osteoclast positive cells were significantly increased,the levels of NO,TNF-α,IL-1β and IL-6 were significantly increased (P<0.05),and the relative expression of RANK and RANKL mRNA was significantly increased (P<0.05).Compared with the model group,in the titanium particles+ERK inhibitor group,the damage degree of bone destruction was alleviated,osteoclast positive cells were reduced,the levels of NO,TNF-α,IL-1β,IL-6 were significantly decreased (P<0.05),and the relative expressions of rank and RANKL mRNA were significantly decreased (P<0.05).Conclusion PD98059,an ERK signaling pathway inhibitor,could significantly reduce the inflammatory osteolysis induced by wear particles,which may be achieved by regulating the RANK/RANKL signaling pathway.