Bone resorption activity of particulate-stimulated macrophages

Authors

  • Tibor T. Glant M.D., Ph.D.,

    Corresponding author
    1. Department of Biochemistry, Rush Medical College at Rush—Presbyterian-St. Luke's Medical Center, Chicago, Illinois
    2. Department of Bioengineering, Clemson University, Clemson, South Carolina
    • Department of Orthopedic Surgery, Rush-Presbyterian-St. Luke's Medical Center, 1653 West Congress Parkway, Chicago, IL 60612
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  • Joshua J. Jacobs,

    1. Department of Orthopedic Surgery, Joint Replacement Program, Rush—Presbyterian—St. Luke's Medical Center, Chicago, Illinois
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  • Gyöngyi Molnár,

    1. Department of Orthopedic Surgery, Joint Replacement Program, Rush—Presbyterian—St. Luke's Medical Center, Chicago, Illinois
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  • Arun S. Shanbhag,

    1. Department of Orthopedic Surgery, Joint Replacement Program, Rush—Presbyterian—St. Luke's Medical Center, Chicago, Illinois
    2. Department of Bioengineering, Clemson University, Clemson, South Carolina
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  • Márta Valyon,

    1. Department of Orthopedic Surgery, Joint Replacement Program, Rush—Presbyterian—St. Luke's Medical Center, Chicago, Illinois
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  • Jorge O. Galante

    1. Department of Orthopedic Surgery, Joint Replacement Program, Rush—Presbyterian—St. Luke's Medical Center, Chicago, Illinois
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Abstract

Particulate wear debris from bone cement or prosthetic components can stimulate macrophages to cause bone resorption in a dose-dependent manner. This bone resorption activity of particulate-stimulated macrophages is associated with increased levels of both prostaglandin E2 (PGE2) and interleukin-1 (IL-1). In this study we compared the effect of particulate size, concentration, and composition on the secretion of IL-1 and PGE2 by peritoneal macrophages and on the bone-resorbing activity of conditioned medium (CM) harvested from particulate-challenged macrophages. Particulates (titanium, Ti; polymethylmethacrylate, PMMA; and polystyrene, PS) only with phagocytosable size stimulated peritoneal macrophages to secrete IL-1 and PGE2 in a dose- and time-dependent manner. Ti particles (1–3 μm) exhibited significantly enhanced bone-resorbing activity measured as 45Ca release. The maximum bone-resorbing response was observed at a concentration of 0.1% Ti (approximately 10–15 Ti particulates per cell), which also corresponded with the highest IL-1 levels measured in particulate-challenged CM. This was measured using either conditioned media from Ti-stimulated macrophages or in cocultures of calvarial bone and macrophages in the presence of Ti. Exogenous PGE2 and recombinant human IL-1 could significantly increase the 45Ca release; indomethacin (IM) significantly reduced both the spontaneous calcium efflux and active 45Ca release from in vivo labeled calvarial bones. However, IM and/or anti-Il-1 antibodies could suppress only partly the macrophage-mediated bone resorption, indicating that, in a macrophage-bone coculture system, factors other than PGE2 and IL-1 also may regulate particulate-induced bone resorption, probably involving multiple cell types.

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