Abstract
Wear particle-induced osteolysis and loosening is a critical process that limits the longevity of total hip arthroplasty. Despite their potential value in the management of aseptic loosening, little is known about the cellular response to bisphosphonates (BPs) in the presence of particulate debris. In the present study, we compared the effect of pamidronate and clodronate, two structurally different bisphosphonates, on the induction of TNF-α release by alumina ceramic (Al2O3) and ultra-high-molecular-weight-polyethylene (UHMWPE) particles. We also looked, by Trypan blue exclusion, at the viability of J774 mouse macrophages incubated with Al2O3 and UHMWPE particles in combination with pamidronate or clodronate. Results showed that pamidronate and clodronate can inhibit UHMWPE particle-induced TNF-α release while they had no effect on Al2O3-stimulated TNF-α release. The co-incubation of pamidronate or clodronate and Al2O3 had no effect on the induction by Al2O3 of poly(ADP-ribose)polymerase (PARP) proteolysis and DNA fragmentation. On the other hand, UHMWPE particles had no effect on these apoptotic markers. However, the co-incubation of pamidronate or clodronate with UHMWPE particles led to the appearance of these markers of apoptosis. Al2O3 and UHMWPE particles had no effect on macrophage cell death or the number of macrophages at the end of experiments. Co-incubation of UHMWPE particles with pamidronate and clodronate led to a significant increase in cell death. Interestingly, the number of macrophages co-incubated with particles and pamidronate or clodronate significantly decreased. In conclusion, our results suggest that the effect of BPs on particle-stimulated macrophages is, at least in part, particle composition dependent.
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Petit, A., Mwale, F., Antoniou, J. et al. Effect of bisphosphonates on the stimulation of macrophages by alumina ceramic particles: A comparison with ultra-high-molecular-weight polyethylene. J Mater Sci: Mater Med 17, 667–673 (2006). https://doi.org/10.1007/s10856-006-9230-x
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DOI: https://doi.org/10.1007/s10856-006-9230-x