Co–Cr wear products derived from metal-on-metal articulations induce apoptosis on monocyte-like U937 cells

Cobalt–chromium alloy (Co–Cr) particles in the nanometre size range are produced by wear at the articulating surfaces of metal-on-metal implants, and are associated with inflammation, bone loss and implant loosening. Additionally, metal implants undergo corrosion inside the human body releasing ions into the surrounding tissue. This led to the withdrawal from the market of the DePuy ASR™ metal-on-metal hip replacements in 2010. Ions released from Co–Cr particles derived from a resurfacing implant and their subsequent cellular up-take have been measured. Moreover, the ability of the metal debris and Cobalt (Co) ions to induce apoptosis was examined. For this purpose, U937 cells and Co pre-treated U937 cells were exposed to Co, metal debris and Co + debris for 24 and 48 h. To measure metal ion concentrations in culture medium and cell lysates Inductively Coupled Plasma Mass Spectrometry (ICP-MS) analysis was performed. Apoptosis was evaluated with Fluorescence-Activated Cell Sorting (FACS) and immunoblotting. The Co–Cr wear debris released significant (p < 0.05) amounts of Co and Chromium (Cr) ions into the culture medium, and there was significant (p < 0.05) cellular uptake of both ions when compared to controls: Co ions were taken up to a greater extent than Cr. Furthermore, there was a significant (p < 0.05) increase in apoptosis after 48 h exposure to wear debris. The debris was more effective as an inducer of apoptosis when cells had been pre-treated with Co ions. This suggests that if a patient receives a second Co–Cr implant it may be more likely to produce adverse effects than the first one.