Enhanced osteolytic potential of monocytes/macrophages derived from bone marrow after particle stimulation.

Abstract

Total hip replacement can be complicated by periprosthetic osteolysis. Monocytes/macrophages play a major role in the formation of the foreign body granulomas induced by wear debris. We hypothesized that periprosthetic monocytes/macrophages do not only accelerate inflammatory and osteoclast-mediated osteolytic processes, but also resorb periprosthetic bone directly by themselves. This study was designed to evaluate the osteolytic potential in vitro of monocytes/macrophages derived from bone marrow. Monocytes/macrophages were produced by filtration of rat bone marrow cells, followed by culture in the presence of macrophage-colony stimulating factor (M-CSF). Monocyte/macrophage properties were ascertained using immunocytochemistry and phagocytic activity. Osteolytic cytokines and extracellular matrix degrading proteinases were quantified at the mRNA level. Adherent cell fraction was immunoreactive for the monocyte/macrophage specific marker CD68 and active in the phagocytosis of carbon particles up to 72 h. They also showed immunoreactivity to cathepsin K, IL-1beta, IL-6, and M-CSF, but mostly did not react to TRAP. mRNA levels of osteolytic cytokines and extracellular matrix degrading proteinases were enhanced, but that of RANKL were not. Monocytes/macrophages resorbed dentine discs and carbonated calcium phosphate was very actively resorbed after stimulation with titanium particles. Harvested bone marrow cells expressed monocyte/macrophage phenotype, but not osteoclastic markers. The capacity of these cathepsin-K-positive phagocytic cells to resorb dentine discs and carbonated calcium phosphate in vitro suggests a direct role of monocytes/macrophages in bone resorption and periprosthetic osteolysis. The finding supports our hypothesis and previous histomorphometric observations on the presence of such osteolytic macrophages in vivo around loosening prosthesis.