RESUMO
PURPOSE: To evaluate the roles of macrophages and their influences on the signal transduction in the periprosthetic osteolysis, the pro-inflammatory signals were analyzed in particles-stimulated macrophages. MATERIALS AND METHODS: Raw 264.7 cell line derived from mice macrophages was used as pre-osteoclasts. To increase the stimulatory effects, the particles were composed of PMMA and polyethylene. Under the similar conditions as osteoclast differentiation, we examined the effect of particles on the pro-inflammatory signals in macrophage: the production of TNF-alpha, the activity of MAPKs (mitogen-activated phosphorylation kinase), the expression of I-kappaB (Inhibitory (B) and the production of H2O2 and nitric oxide. RESULTS: The particles stimulated the secretion of TNF-alpha and increased the phosphorylation of p38 and ERK in course of time. The concentration of H2O2 was increased; however the nitric oxide formation was not increased by particle treatment. In addition, the production of H2O2 was synergistically increased by suboptimal stimulation with PMA (phorbol 12-myristate 13-acetate). Expressions of I-kappaB were inhibited by particles. CONCLUSION: The particles may stimulate the activation of MAPKs, the production of TNF-alpha, reactive oxygen species (ROS) and the activation of NF-kappaB in the pre-osteoclasts. We speculate that particles may mediate the pro-inflammatory signal cascade by the activation of NF-kappaB through ROS in pre-osteoclasts, rather than reactive nitrogen species (RNS). Therefore we suggest that the macrophages in inflammatory osteolysis may have the characteristics of pre-osteoclast as well as pro-inflammatory cell. Further researches should be recommended.