Effects of sublethal metal ion concentrations on osteogenic cells derived from bone marrow stromal cells

Ions released from implant surfaces are suspected of playing some role in osteolysis surrounding metal prostheses. To understand how ions may affect osteogenesis, previous work exposed osteogenic cells to metal ions to study acute cytotoxic responses. The purpose of this study was to assess the long-term effects of sublethal ion concentrations on osteogenic cell proliferation and function. Bone marrow stromal cells were harvested from juvenile rats and exposed to solutions of ions associated with Co-Cr-Mo and Ti-6Al-4V implants. Cells were cultured for up to 4 weeks and assayed for total protein, alkaline phosphatase, osteocalcin, and calcium. Other than V+5, none of the ions affected cell proliferation, indicating that the chosen concentrations were sublethal as desired. V+5 elicited delayed gross toxicity not previously observed during acute experiments. At the chosen concentrations, Co+2, Cr+6, Mo+6, and Co-Cr-Mo alloy elicited little effect on cell proliferation and moderate effects on matrix mineralization. Cultures exposed to Ti+4, Al+3, and Ti-6Al-4V alloy also showed no decrease in cell number, but did show near total suppression of osteocalcin secretion and matrix mineralization. These results suggest that ions released from Ti alloy implants may interfere with osteoblastic cell differentiation, contributing to periprosthetic osteolysis by impairing normal osteogenesis.