RELATIVE ROLES OF OSTEOCLAST COLONY-STIMULATING FACTOR AND MACROPHAGE-COLONY-STIMULATING FACTOR IN THE COURSE OF OSTEOCLAST DEVELOPMENT

Although recent studies have shown that osteopetrotic (op/op) mice lac k macrophage colony-stimulating factor (M-CSF or CSF-1), the precise r ole of M-CSF in the development of immature osteoclasts remains unknow n. Using a recently discovered osteoclast-specific colony-stimulating factor (O-CSF) and in vitro long-term bone marrow culture systems, we investigated the ability of op/op and control marrow stromal cells to support the production of O-CSF-responsive clonogenic osteoclast proge nitors (colony-forming unit-osteoclast [CFU-O]) from inoculated normal stem cells. Remarkably, op/op stromal cell cultures produced five tim es as many nonadherent cells as control cultures throughout the experi mental period of 14 weeks; an average of 37% of these cells were nonvi able compared with 8% in control cultures. Significantly higher number s of CFU-O were found in op/op cultures than in control cultures; the CFU-O in op/op and control cultures were proliferating at a similar ra te. Higher numbers of calcitonin receptor-bearing cells were found whe n harvested cells from op/op flasks were cultured with 1,25(OH)(2)D-3. These studies clearly show that op/op marrow stromal cells can suppor t the differentiation and proliferation of osteoclast progenitors from inoculated stem cells and provide the first experimental evidence tha t M-CSF is not essential for the early stages of osteoclast developmen t. We hypothesize that while O-CSF supports proliferation of osteoclas t progenitors, M-CSF plays a role in the later development and maturat ion of the progenitor as well as in the prevention of cell death.