Bone resorption activity of particulate-stimulated macrophages.
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 microns) 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.
Glant
T T
TT
Department of Biochemistry, Rush Medical College at Rush-Presbyterian, St. Luke's Medical Center, Chicago, Illinois.
Jacobs
J J
JJ
Molnár
G
G
Shanbhag
A S
AS
Valyon
M
M
Galante
J O
JO
D000818:Animals; D001862:Bone Resorption / Q000139:chemically induced / Q000503:physiopathology*; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D017077:Culture Media, Conditioned; D015232:Dinoprostone / Q000378:metabolism / Q000494:pharmacology; D005260:Female; D007213:Indomethacin / Q000494:pharmacology; D007375:Interleukin-1 / Q000378:metabolism / Q000494:pharmacology; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D008768:Methylmethacrylates / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009924:Organ Culture Techniques; D010316:Particle Size; D010587:Phagocytosis; D011137:Polystyrenes / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000494:pharmacology; D014025:Titanium / Q000494:pharmacology*
D017077:Culture Media, Conditioned; D007375:Interleukin-1; D008768:Methylmethacrylates; D011137:Polystyrenes; D011994:Recombinant Proteins; D014025:Titanium; D015232:Dinoprostone; D002118:Calcium; D007213:Indomethacin