Abstract
Introduction: Despite a resurgence in cobalt-chromium metal-on-metal arthroplasty, the potential toxicity of metal ions in the periprosthetic area remains a cause for concern. Studies to date have assessed the acute effect of cobalt ions on osteoblasts over 48 hours. The aim of our study was to determine the response of osteoblasts to cobalt ions over a prolonged period of exposure.
Methods. Primary human osteoblasts were cultured and treated with cobalt (10ppm) over 21 days. Osteoblast function was assessed via alkaline phosphatase activity and calcium deposition. ELISA were used to assess chemokine (IL-8, MCP-1 and TNF-α) secretion. Osteoblast gene expression was assessed using microarray analysis and real time PCR. Immunoflourescent cell staining of actin filaments was used to examine osteoblast morphology.
Results: Chemokine (IL-8) secretion by osteoblasts was significantly increased after 10 days of stimulation with cobalt ions. In parallel with this, osteoblast function was also significantly inhibited as demonstrated by reduced alkaline phosphatase activity and calcium deposition. Regarding osteoblast phenotype, FSP-1, CTGF and TGF-β gene expression were upregulated indicating a transition in osteoblast phenotype. Immunoflourescent staining of actin filaments also showed a change in osteoblast morphology. Taken together, these data show cobalt ions induce a change in the osteoblast phenotype to that of a mesenchymal cell type.
Conclusion: After 10 days of treatment with cobalt ions, osteoblasts no longer function as osteogenic cells. they undergo transition to a mesenchymal cell type. Furthermore, IL-8 secretion is increased which attracts neutrophils to the periprosthetic area thereby contributing to the inflammatory response that characterises osteolysis.
Correspondence should be addressed to Mr Richard Wallace at Musgrave Park Hospital, 20 Stockman’s Lane, Belfast BT9 7JB, Northern Ireland.
