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Chemokine gene activation in human bone marrow‐derived osteoblasts following exposure to particulate wear debris
Author(s) -
Fritz Elizabeth A.,
Glant Tibor T.,
Vermes Csaba,
Jacobs Joshua J.,
Roebuck Kenneth A.
Publication year - 2006
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.30609
Subject(s) - osteoblast , chemokine , materials science , microbiology and biotechnology , interleukin 8 , cytokine , cancer research , immunology , chemistry , inflammation , biology , biochemistry , in vitro
Particulate wear debris induces the expression of pro‐inflammatory cytokine and chemokine genes in various cell types of the periprosthetic region. We have previously reported that titanium particles stimulate the selective induction of interleukin‐8 (IL‐8) and monocyte chemoattractant protein‐1 (MCP‐1) chemokines in human osteoblast‐like osteosarcoma cells. In this study, we characterize the human bone marrow‐derived osteoblast chemokine response to titanium particles. We demonstrate that titanium particles result in enhanced IL‐8 and MCP‐1 protein secretion as well as differential chemokine gene activation. Osteoblast chemokine expression was regulated at the level of gene transcription, with a time‐dependent induction of NF‐κB activation. Inhibition studies with N ‐acetyl‐ L ‐cysteine (Nac) and MG‐132 suggest that titanium particle activation of NF‐κB activity and IL‐8 chemokine exression involves oxidant signaling and IκBα‐proteasomal degradation. Activation of the NF‐κB transcription factor, as well as the IL‐8 gene, are redox‐regulated. We also demonstrate that while cytochalasin D, a potent inhibitor of phagocytosis, suppressed the titanium particle effect on IL‐8 protein release in human bone marrow‐derived osteoblasts, the inhibitor had no effect on IL‐8 expression in MG‐63 osteoblast‐like cells. Collectively, these results provide insight into the potential mechanisms responsible for the particulate activation of osteoblast chemokine expression and suggest an important role for the osteoblast in the pathogenesis of periprosthetic osteolysis. © 2005 Wiley Periodicals, Inc. J Biomed Mater Res, 2006