Direct influence of titanium and zirconia particles on the morphology and functionality of mature human osteoclasts

Within the last ten years of biomedical implants, the focus is increasingly on bioceramics, specifically on zirconia (ZrO2). Hence, we analyzed the impact of zirconia particles in comparison to titanium (cpTi) particles on mature human osteoclasts (OCs) as little is known about the direct effect of wear particles on mature OCs and their role in the osteolytic process during aseptic endoprosthesis loosening. Changes in cell morphology and functionality of OCs incubated with particles in different concentrations were investigated. OCs tend to be enlarged after three days of cultivation with both types of particles, especially with high concentrations of ZrO2, suggesting increased cell fusion. Further, we identified significantly increased expression of osteoclast specific and bone matrix related genes: VNR, RANK, TRAP and CTSK pointing on a direct stimulatory particle effect on the functionality of mature OCs. In completion, we quantified the bone resorption activity of particle treated mature OCs but could not detect a significant difference in bone resorption compared to osteoclasts cultivated without particles. However, we could identify significantly higher gene expression of MMP-1 in particle treated OCs compared to untreated control OCs after three days of incubation. We also detected an impaired production of the tissue inhibitor of metalloproteinase TIMP-1, especially for OCs treated with high ZrO2 concentrations. In conclusion, our in vitro data show that abrasion particles could have a direct influence on mature osteoclasts and therefore could promote increased OC-mediated bone resorption during aseptic loosening of total joint replacements. This article is protected by copyright. All rights reserved.