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.

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).

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%.

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.