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Metallic wear debris may regulate CXCR4 expression in vitro and in vivo
Author(s) -
Drynda Andreas,
Singh Gurpal,
Buchhorn Gottfried H.,
Awiszus Friedemann,
Ruetschi Marcel,
Feuerstein Bernd,
Kliche Stefanie,
Lohmann Christoph H.
Publication year - 2015
Publication title -
journal of biomedical materials research part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.849
H-Index - 150
eISSN - 1552-4965
pISSN - 1549-3296
DOI - 10.1002/jbm.a.35330
Subject(s) - osteolysis , stromal cell , cxcr4 , chemokine , blot , in vivo , tumor necrosis factor alpha , stromal cell derived factor 1 , downregulation and upregulation , materials science , chemokine receptor , cancer research , microbiology and biotechnology , receptor , medicine , biology , biochemistry , gene , surgery
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. © 2014 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 103A: 1940–1948, 2015.