In a previous study, using co-cultures of embryonic bone rudiments stripped of periosteum, and mononuclear phagocytes of various sources, we found that multinucleated
mineral-resorbing osteoclasts developed in vitro from radiosensitive mouse bone marrow mononuclear phagocytes (
BMMP). (Burger, E. H., J. W. M. van der Meer, J. S. van de Gevel, C. W. Thesingh, and R. van Furth, 1982, J. Exp. Med. 156:1604-1614). In the present study, this co-culture technique was used to analyze the influence of bone-forming cells on osteoclast formation and
bone resorption by
BMMP or peritoneal exudate cells (PEC).
BMMP or PEC were co-cultured with liver or dead bone, i.e., in the presence or absence of liver bone-forming cells.
Mineral resorption and osteoclast formation were monitored via 45Ca release from prelabeled live or dead bone followed by histology. Osteoclasts developed from precultured
BMMP as indicated by [3H]
thymidine labeling, but only in live and not in dead bone. They formed readily from
BMMP but only erratically, and after a longer culture period, from PEC. Macrophages from
BMMP and PEC invaded live and dead bone rudiments but did not resorb the intact mineralized matrix. In contrast, ground bone
powder was resorbed avidly by both cell populations, without formation of osteoclasts. We conclude that live bone-forming cells are required for osteoclast formation from progenitors. Live bone is only resorbed by osteoclasts, and not by macrophages. Osteoclast progenitors are abundant in cultures of
BMMP but scarce in PEC, which makes a direct descendance of osteoclasts from mature macrophages unlikely.