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J Biomed Mater Res A. 2015 Jun;103(6):1940-8. doi: 10.1002/jbm.a.35330. Epub 2014 Sep 17.

Metallic wear debris may regulate CXCR4 expression in vitro and in vivo.

Author information

1
Department of Orthopaedic Surgery, Otto-von-Guericke University, Magdeburg, Germany.

Abstract

CXCR4, the chemokine receptor for CXCL12, also known as SDF-1 (stromal cell derived factor-1), has been shown to play a pivotal role in bone metastasis, inflammatory, and autoimmune conditions but has not been investigated in periprosthetic osteolysis. We co-cultured osteoblast-like cells with increasing concentrations of metallic (Co-35Ni-20Cr-10Mo and Co-28Cr-6Mo) and Co-ions simulating wear debris. Real-time polymerase chain reaction (RT-PCR) and Western blotting were used to quantify gene and protein expression of CXCR4. The expression of tumor necrosis factor-alpha (TNF-α) and the effects of AMD3100 (bicyclam) on both CXCR4 and TNF-α expression among these cells was investigated. RT-PCR showed an increase in CXCR4 mRNA (7.5-fold for MG63 and 4.0-fold for SaOs-2 cells) among cells co-cultured with metal alloy particles. Western blotting showed a time-dependent increase in protein expression of CXCR4. The attempted blockade of CXCR4 by its known competitive receptor agonist AMD3100 led to a significant inhibition TNF-α mRNA expression. Immunohistochemistry showed CXCR4 positivity among patients with failed metal-on-metal hip replacements and radiographic evidence of osteolysis. Our data collectively suggest that the CXCR4 chemokine is upregulated in a dose- and time-dependent manner in the presence of metallic wear debris.

KEYWORDS:

chemokine receptors; cobaltchromium alloys; metallic debris; orthopedic implants

PMID:
25205627
DOI:
10.1002/jbm.a.35330
[Indexed for MEDLINE]

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