MEDIATOR INTERACTIONS IN MACROPHAGE PARTICULATE BONE-RESORPTION

The purpose of this study was to examine the mechanism by which mediat ors released from macrophages exposed to cement particles may interact with cells in bone to ultimately lead to bone resorption. Macrophages were exposed to cement particles, and then this conditioned medium wa s exposed to rat calvarial bones in vitro. The macrophage conditioned medium contained increased levels of tumor necrosis factor, but not in terleukin 1 or prostaglandin E(2). Exposure of this medium to the calv aria led to release of prostaglandin E(2) by the calvaria, but not tum or necrosis factor or interleukin 1. Bone resorption was assessed by m easuring the release of calcium 45 from the newborn rat calvarial bone s. At 48, 72, and 96 h of incubation, the macrophage/cement particle-c onditioned medium led to the release of both prostaglandin E(2) and ca lcium 45 from the calvaria. To determine whether the release of calciu m 45 was dependent on prostaglandin E(2) production by the cells in bo ne, the calvaria were incubated with 600 ng/ml of indomethacin in addi tion to the macrophage-conditioned medium. The addition of indomethaci n was effective in inhibiting both prostaglandin E(2) and calcium 45 r elease from the calvaria, even after 96 h of exposure to the macrophag e-conditioned medium. This study suggests that tumor necrosis factor p roduced in association with macrophage/cement particle osteolysis aris es from macrophages and not cells in bone, and that prostaglandin E(2) originates from cells in bone and not from macrophages. Interleukin 1 was not found to be produced by macrophages or bone, and appears to h ave a lesser role. This study also suggests that the production of pro staglandin E(2) by cells in bone plays an important role in the bone r esorption which accompanies aseptic loosening. Macrophage exposure to bone-cement particles leads to the release of mediators which stimulat es bone resorption, at least in part, through a prostaglandin E(2)-dep endent mechanism. (C) 1995 John Wiley & Sons, Inc.