LOCAL CONCENTRATIONS OF MACROPHAGE-COLONY-STIMULATING FACTOR MEDIATE OSTEOCLASTIC DIFFERENTIATION

Macrophage colony-stimulating factor (M-CSF) is essential for differen tiation of osteoclasts and macrophages from a common bone marrow precu rsor. Using ST-2 stromal cell/murine bone marrow coculture, we studied the effects of increasing amounts of M-CSF on differentiation of macr ophages and osteoclasts. Addition of exogenous M-CSF caused a dose-dep endent 98% decrease in tartrate-resistant acid phosphatase (TRAP)posit ive multinucleated cells, accompanied by a 2.5-fold increase in nonspe cific esterase-staining macrophages. Similar decreases in osteoclastic functional activity, including I-125-labeled calcitonin binding and c alcitonin-stimulated adenosine 3',5'-cyclic monophosphate (cAMP) produ ction, were observed. Addition of exogenous M-CSF beyond 6 days in coc ulture had a decreasing ability to inhibit osteoclast formation, sugge sting that M-CSF exerts its effects early in osteoclast differentiatio n, during the proposed proliferative phase of osteoclast formation. Si milarly, early addition of neutralizing anti-M-CSF inhibited osteoclas t formation, with diminishing effects beyond day 9. These results sugg est that local high concentrations of M-CSF may influence the early de termination of terminal differentiation into either macrophages or ost eoclasts.