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We co\u2010cultured osteoblast\u2010like cells with increasing concentrations of metallic (Co\u201035Ni\u201020Cr\u201010Mo and Co\u201028Cr\u20106Mo) and Co\u2010ions simulating wear debris. Real\u2010time polymerase chain reaction (RT\u2010PCR) and Western blotting were used to quantify gene and protein expression of CXCR4. The expression of tumor necrosis factor\u2010alpha (TNF\u2010\u03b1) and the effects of AMD3100 (bicyclam) on both CXCR4 and TNF\u2010\u03b1 expression among these cells was investigated. RT\u2010PCR showed an increase in CXCR4 mRNA (7.5\u2010fold for MG63 and 4.0\u2010fold for SaOs\u20102 cells) among cells co\u2010cultured with metal alloy particles. Western blotting showed a time\u2010dependent increase in protein expression of CXCR4. The attempted blockade of CXCR4 by its known competitive receptor agonist AMD3100 led to a significant inhibition TNF\u2010\u03b1 mRNA expression. Immunohistochemistry showed CXCR4 positivity among patients with failed metal\u2010on\u2010metal hip replacements and radiographic evidence of osteolysis. Our data collectively suggest that the CXCR4 chemokine is upregulated in a dose\u2010 and time\u2010dependent manner in the presence of metallic wear debris. \u00a9 2014 Wiley Periodicals, Inc. 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