Mediator interactions in macrophage/particulate bone resorption

Abstract

The purpose of this study was to examine the mechanism by which mediators 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 was exposed to rat calvarial bones in vitro. The macrophage conditioned medium contained increased levels of tumor necrosis factor, but not interleukin 1 or prostaglandin E₂. Exposure of this medium to the calvaria led to release of prostaglandin E₂ by the calvaria, but not tumor necrosis factor or interleukin 1. Bone resorption was assessed by measuring the release of calcium 45 from the newborn rat calvarial bones. At 48, 72, and 96 h of incubation, the macrophage/cement particle‐conditioned medium led to the release of both prostaglandin E₂ and calcium 45 from the calvaria. To determine whether the release of calcium 45 was dependent on prostaglandin E₂ production by the cells in bone, the calvaria were incubated with 600 ng/ml of indomethancin in addition to the macrophage‐conditioned medium. The addition of indomethacin was effective in inhibiting both prostaglandin E₂ and calcium 45 release from the calvaria, even after 96 h of exposure to the macrophage‐conditioned medium. This study suggests that tumor necrosis factor produced in association with macrophage/cement particle osteolysis arises from macrophages and not cells in bone, and that prostaglandin E₂ originates from cells in bone and not from macrophages. Interleukin 1 was not found to be produced by macrophages or bone, and appears to have a lesser role. This study also suggests that the production of prostaglandin E₂ by cells in bone plays an important role in the bone resorption which accompanies aseptic loosening. Macrophage exposure to bone‐cement particles leads to the release of mediators which stimulates bone resorption, at least in part, through a prostaglandin E₂‐dependent mechanism. © 1995 John Wiley & Sons, Inc.