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 indomethacin 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.(ABSTRACT TRUNCATED AT 250 WORDS)

Bone-resorbing cytokines in serum of patients with aseptic loosening of hip prostheses

“…Those with a TiAlV cemented prosthesis showed a significant increase in levels of IL-1␤ and also had the highest levels of IL-6. These data agree with the results of other authors, who showed that TiAlV 7,18,19 and polymethylmethacrylate particles 20 in vitro induced the release of inflammatory cytokines in monocyte/macrophages. The highest cytokine concentrations were observed in the group of patients treated with NSAIDs.…”

The effects of cobalt chromium upon macrophages

“…7,8,23 In prior studies from this laboratory, conditioned media obtained from macrophages exposed to PMMA particles were able to stimulate 45 Ca release from radiolabeled calvaria even without an additional osteoblast contribution. 18 In addition, in previous studies using this cell line, TNF-␣ was identified as being the principle mediator released from macrophages exposed to PMMA particles which was necessary to stimulate 45 Ca release from labeled calvaria. 20 It is speculated that the difference between the boneresorbing ability of media obtained from macrophages 45 Ca release.…”

“…This finding is consistent with the results of other studies in which the mechanism by which particulate exposure to macrophages leads to mediator release and osteoclast recruitment is dependent upon the presence of osteoblasts. 16,18,24,25 Exposure of macrophages to cobalt chromium particles was toxic, as reflected by release of LDH. This is also consistent with the results of Haynes et al, 22 who also found significant toxicity associated with these particles.…”

“…1985) were observed. Bone resorption was determined by a modified version of the method of Horowitz and Purdon 18 and Reynolds and Dingle. 19 Pregnant Sprague-Dawley rats (Charles River, Portage, MI) at approximately 16-18 days gestation were injected subcutaneously with 500 Ci of 45 CaCl 2 (New England Nuclear, Boston, MA).…”

Immunotoxicity of Medical Devices

“…Examples of these are prototypes of inflammatory cells such as peripheral blood monocytes, lymphocytes, and fibroblastic cells (Rae et al, 1979;Goldring et al, 1990;Giant et al, 1993;Horowitz et al, 1991Horowitz et al, , 1995Haynes etal, 1993;Frondoza etal, 1994;Shanbhag etal, 1995;Gonzales etal, 1996). Cells retrieved from tissues or blood which are maintained in short-term culture for immediate use are thought to most closely express their original tissue characteristics or "phenotype."…”