The cytotoxicity of chromium in osteoblasts: effects on macromolecular synthesis

Exposure of an immortalized rat osteoblast cell line, FFC cells, to Cr VI resulted in inhibition of protein, DNA and RNA synthesis. Protein synthesis (^3\hbox{H}-leucine incorporation) was most sensitive. There was no inhibition of the incorporation of ^{3}\hbox{H}-proline into collagen at the concentrations which inhibited general protein synthesis (1 muM), but synthesis of extracellular collagen fibers was markedly decreased by concentrations of 0.5 muM Cr VI and above. This indicates that some aspect of the post-translational processing of the collagen fibers is sensitive to Cr VI inhibition. Collagen fiber formation was not inhibited by Cr III (which does not penetrate the cell membrane) or when Cr VI was reduced to Cr III extracellularly. This suggests that the Cr VI inhibits an intracellular stage of post-translational collagen processing. Both Cr VI and Cr III inhibit collagenase activity, the former being more potent but less efficacious. Our results suggest that leakage of chromium ions from orthopedic implants may cause a decrease in the proliferation and infiltration of osteoblasts around the implant, and a reduction in the synthesis and altered turnover of collagen in extracellular matrix. These effects will influence the osseointegration of implants, the osteolytic response, and ultimately the stable life-time of the implants.