Abstract
Metal-on-metal (MoM) bearing technology, made of cobalt-chromium (Co-Cr) alloys, is being used in anticipation of extending the durability of hip replacements. Increasingly, concern has been expressed that long term exposure to Co2+ and Cr3+ could cause DNA damage and immune dysfunction; specifically a reduction in the circulating number of CD8+ cytotoxic cells. More recently, we reported that Co2+ and Cr3+ affected the differentiation of osteoclast precursors into bone-resorbing osteoclasts. Despite these observations the effects of metal ions on osteoblast activity have been poorly investigated. The aim of the current study was to elucidate the effects of various metal ions on osteoblast activity in vitro.
Cells of the human osteosarcoma cell line SaOS-2 were cultured in the presence of 0, 1, 10 and 100 μM Co2+ and Cr3+. The morphology, viability, cytokine release (TNFalpha, IL-1beta, IL-6, LIGHT, MIP-1alpha and VEGF) and alkaline phosphatase activity were investigated after 24h and 48h in contact with metal ions. Finally the capacity of SaOS-2 to produce and mineralize a new bone matrix was assessed by the Alizarin red method. All experiments were repeated at least 5 times and the differences between each were determined using non-parametric Mann-Whitney test.
Compared to untreated cultures, although the morphology looked normal after 48h, the viability indicated that Co2+ and Cr3+ ions at high concentrations induced some significant and irreversible damages to the osteoblast cells. Interestingly, any of the cytokines investigated were released in contact with metal ions after 24h or 48h. The alkaline phosphatase activity was significantly increased by low concentrations of Co2+ and decreased by high concentrations of Cr3+ after 24h and 48h. Moreover, the degree of mineralization of a new bone matrix in vitro was significantly reduced when the SaOS-2 cells were exposed to high concentrations of Cr3+, but significantly increased when they were exposed to Co2+.
Our results indicated that irreversible damages are caused to the cells as soon as 24h with high concentrations of metal ions. For osteoblasts cells, Co2+ appeared to be less toxic than Cr3+ at high concentrations.
This study was supported by Furlong Research Charitable Foundation
Correspondence should be addressed to Dr Roger Bayston, Division of Orthopaedic and Accident Surgery, Queen’s Medical Centre, Nottingham, NG7 2UH, England.
