Periprosthetic osteolysis: Characterizing the innate immune response to titanium wear-particles

Authors

  • Christine A. St. Pierre,

    1. Department of Medicine, University of Massachusetts Medical School, Lazare Research Building, Room 228, 364 Plantation Street, Worcester, Massachusetts 01605
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  • Melvin Chan,

    1. Department of Medicine, University of Massachusetts Medical School, Lazare Research Building, Room 228, 364 Plantation Street, Worcester, Massachusetts 01605
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  • Yoichiro Iwakura,

    1. Center for Experimental Medicine and Systems Biology, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan
    2. Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Agency, Saitama 332-0012, Japan
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  • David C. Ayers,

    1. Department of Orthopedics, University of Massachusetts Medical School, Worcester, Massachusetts 01605
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  • Evelyn A. Kurt-Jones,

    1. Department of Medicine, University of Massachusetts Medical School, Lazare Research Building, Room 228, 364 Plantation Street, Worcester, Massachusetts 01605
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  • Robert W. Finberg

    Corresponding author
    1. Department of Medicine, University of Massachusetts Medical School, Lazare Research Building, Room 228, 364 Plantation Street, Worcester, Massachusetts 01605
    • Department of Medicine, University of Massachusetts Medical School, Lazare Research Building, Room 228, 364 Plantation Street, Worcester, Massachusetts 01605. T: 508-856-1886; F: 508-856-6176.
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Abstract

Osteolysis of bone following total hip replacement is a major clinical problem. Examination of the areas surrounding failed implants has indicated an increase in the bone-resorption-inducing cytokine, interleukin 1β (IL-1β). NALP3, a NOD-like receptor protein located in the cytosol of macrophages, signals the cleavage of pro-IL-1β into its mature, secreted form, IL-1β. Here we showed that titanium particles stimulate the NALP3 inflammasome. We demonstrated that titanium induces IL-1β secretion from macrophages. This response depended on the expression of components of the NALP3 inflammasome, including NALP3, ASC, and Caspase-1. We also showed that titanium particles trigger the recruitment of neutrophils and that this acute inflammatory response depends on the expression of the IL-1 receptor and IL-1α/β. Moreover, administration of the IL-1 receptor antagonist (IL-1Ra) diminished neutrophil recruitment in response to titanium particles. Together, these results suggest that titanium particle-induced acute inflammation is due to activation of the NALP3 inflammasome, which leads to increased IL-1β secretion and IL-1-associated signaling, including neutrophil recruitment. Efficacy of IL-1Ra treatment introduces the potential for antagonist-based therapies for implant osteolysis. © 2010 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 28:1418–1424, 2010

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