MURINE MACROPHAGE PRECURSOR CELL-LINES ARE UNABLE TO DIFFERENTIATE INTO OSTEOCLASTS - A POSSIBLE IMPLICATION FOR OSTEOCLAST ONTOGENY

Six murine macrophage precursor cell lines, thought to be arrested aro und the CFU-GM stage of the myeloid differentiation and shown to be ne gative for acid phosphatase, F4/80 antigen expression and phagocytosis capacity, were tested for their ability to differentiate into osteocl asts. Their differentiation potential was compared with that of the ha emopoietic stem cell line FDCP-mix C2GM. None of the macrophage precur sor cell lines could be induced to differentiate into osteoclasts when the cells were cocultured with either periosteum-free metatarsal bone s of fetal mice, or monolayers of osteoblast-like cells. In contrast, when the haemopoietic stem cell line FDCP-mix C2GM, murine fetal liver cells or murine spleen cells were used as a source of haemopoietic pr ecursor cells, numerous osteoclasts were formed in both culture system s. During cell culture a small percentage of the macrophage precursor cells attached to the bottom of the culture well. These firmly attache d cells acquired acid phosphatase activity, F4/80 antigen expression a nd phagocytosis capacity. Furthermore, when the cell lines were cultur ed for 2 or 4 days with 1% DMSO, up to 30% of the precursor cells diff erentiated into metamyelocytes. These results suggest that the macroph age precursor cell lines are able to acquire macrophage and granulocyt e characteristics, but are unable to differentiate into osteoclasts. I n contrast, the haemopoietic stem cell line FDCP-mix C2GM is able to d ifferentiate into both macrophages and osteoclasts. We therefore sugge st that the osteoclast lineage branches off at an early stage of the m yeloid differentiation pathway.