Mononuclear phagocytes secrete a protein that directly resorbs devitalized bone particles.

: The radiolabelled bone particle assay was used as an in vitro model of bone resorption. Normal human peripheral blood monocytes and the monoblastic cell line, U937, increased 45Ca release from the devitalized bone particles. In contrast, normal human peripheral blood neutrophils, resting or stimulated, did not increase 45Ca release. Exposure of monocytes to gamma interferon (INF-gamma) stimulated secretion of hydrogen peroxide and inhibited 45Ca release from bone particles. U937 cells incubated with 1,25(OH)2D3 and lymphokines had increased secretion of oxygen reduction products and increased 45Ca release. Medium conditioned by incubation with U937 cells stimulated 45Ca release to the same extent as the U937 cells. The 45Ca releasing activity in the medium was resistant to extremes of temperature and acidification. This activity is not dependent on the presence of disulfide bonds and was not inhibited by collagenase or trypsin inhibitors. Exposure to a proteolytic agent reduced the activity by over 50%. These findings are consistent with the concept that mononuclear phagocytes secrete a substance, presumably a protein, which acts directly on the bone particles. The isolation and identification of this substance may increase our understanding of the mechanisms of bone loss associated with inflammatory processes.