Activation of Transcription Factor NF-kappaB and c-Jun/AP-1 by Various Compositions of Particles in Osteoclast Precursor Cells

ABSTRACT

PURPOSE: This study was performed in order to investigate the effects of various particle preparations on NF-kappaB and c-Jun/AP-1 activity in osteoclast precursor cells. MATERIALS AND METHODS: Osteoclast precursor cells isolated from C57BL mice were treated with PMMA (polymethylmethacrylate) spheres, polystyrene, titanium particles, and retrieved metal particles from failed cementless total hip replacements. NF-kappaB and c-Jun/AP-1 DNA binding activities were analyzed using electrophoretic mobility shift assays (EMSA). RESULTS: Commercially available PMMA and polystyrene spheres routinely showed negativity on endotoxin assays, but titanium particles and retrieved metal particles consistently showed positivity. PMMA spheres, with a maximal response noted at 30 minutes with an optimal concentration of 0.6 mg/ml, were potent stimulator of NF-kappaB and c-Jun/AP-1 activity in osteoclast precursor cells. Other particles (polystyrene, titanium, metal retrievals) also activated transcription factor NF-kappaB and c-Jun/AP-1 compared to controls. Endotoxin removal from retrieved metal particles diminished the biologic effect by approximately 40%. CONCLUSION: Particles of various compositions and sizes (PMMA, polystyrene, titanium, and retrieved metal particles) activated the NF-kappaB and c-Jun/AP-1 signaling pathways. This suggests that NF-kappaB and c-Jun/AP-1 may have important roles in the pathogenesis of periprosthetic osteolysis.