Bone solubilization by mononuclear cells.

Mononuclear cells derived from chicken peripheral blood or from thioglycollate-induced mouse peritoneal exudates were found to cause calcium release from devitalized homologous bone in vitro. These mononuclear cells with osteolytic activity were adherent to plastic surfaces and were identified as being macrophages by cell surface markers and histochemical staining. Other mononuclear cells such as chicken thymocytes, nonadherent peripheral blood mononuclear cells, and chick embryo fibroblasts did not cause bone dissolution. In parallel with the active solubilization of bone mineral, 14C-label was also released from devitalized calvaria prelabeled with 14C-proline. Macrophages, inactivated by repeated freezing and thawing as well as those cultured in the presence of iodoacetate, did not solubilize bone in vitro. The degree of bone solubilization was directly related to the numbers of macrophages per culture as well as the duration of the culture period. Powdered devitalized homologous bone was used in most experiments, but macrophages were also able to solubilize bone material in vitro from devitalized calvaria and bone slabs. The addition of Escherichia coli lipopolysaccharide to cultures of bone and macrophages significantly increased the levels of calcium released from bone. The addition of parathyroid hormone and calcitonin had no effect on macrophage-mediated bone dissolution. These results suggest that viable macrophages have osteolytic activity and that this activity is modulated by an inflammatory mediator, endotoxin.