MACROPHAGE-COLONY-STIMULATING FACTOR STIMULATES SURVIVAL AND CHEMOTACTIC BEHAVIOR IN ISOLATED OSTEOCLASTS

Macrophage colony-stimulating factor (M-CSF) is known to play an impor tant role in osteoclast formation. However, its actions on mature cell s have not been fully characterized. We now report that M-CSF dramatic ally stimulates osteoclastic motility and spreading; osteoclasts respo nded to a gradient of M-CSF with orientation, and random cell polariza tion occurred after isotropic exposure. M-CSF also supported the survi val of osteoclasts by preventing apoptosis. Paradoxically, M-CSF inhib its bone resorption by isolated osteoclasts. We found that this was ef fected predominantly by reduction in the number of excavations. Thus, M-CSF showed a propensity to suppress resorption through a reduction i n the proportion of cells that were resorbing bone. Our data suggest t hat apart from the established role of M-CSF in the provision of precu rsors for osteoclastic induction, a major role for M-CSF in bone resor ption is to enhance osteoclastic survival, migration, and chemotaxis. It seems appropriate that during these processes resorptive functions should be suppressed. We suggest that M-CSF continues to modulate oste oclastic activity once osteoclasts are on resorptive sites, through re gulation of the balance between resorption and migration, such that no t only the quantity, but the spatial pattern of resorption can be cont rolled by adjacent M-CSF-secreting cells of osteoblastic lineage.