title: Metallic wear debris may regulate CXCR4 expression in vitro and in vivo.
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.
authors.affiliation: Department of Orthopaedic Surgery, Otto-von-Guericke University, Magdeburg, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Drynda
authors.forename: Gurpal
authors.initials: G
authors.lastname: Singh
authors.forename: Gottfried H
authors.initials: GH
authors.lastname: Buchhorn
authors.forename: Friedemann
authors.initials: F
authors.lastname: Awiszus
authors.forename: Marcel
authors.initials: M
authors.lastname: Ruetschi
authors.forename: Bernd
authors.initials: B
authors.lastname: Feuerstein
authors.forename: Stefanie
authors.initials: S
authors.lastname: Kliche
authors.forename: Christoph H
authors.initials: CH
authors.lastname: Lohmann
mesh_terms: D000368:Aged; D000497:Alloys / Q000494:pharmacology; D015153:Blotting, Western; D002460:Cell Line; D003035:Cobalt / Q000494:pharmacology; D003710:Demography; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D061825:Metal-on-Metal Joint Prostheses / Q000009:adverse effects; D008670:Metals / Q000009:adverse effects*; D008875:Middle Aged; D010006:Osteoblasts / Q000378:metabolism; D019736:Prostheses and Implants / Q000009:adverse effects*; D019718:Receptors, CXCR4 / Q000235:genetics / Q000378:metabolism*
chemical_list: D000497:Alloys; D008670:Metals; D019718:Receptors, CXCR4; D003035:Cobalt
keywords: chemokine receptors; cobaltchromium alloys; metallic debris; orthopedic implants