Macrophage colony-stimulating factor restores bone resorption in op/op bone in vitro in conjunction with parathyroid...

The in vivo administration of macrophage colony-stimulating factor (M-CSF) restores osteoclastogenesis and bone resorption in the op/op murine osteopetrosis. In vitro, exogenous M-CSF has been shown to be necessary for the generation of osteoclast-like cells in cocultures of hematopoietic and mesenchymal cells obtained from this mutant. In this study we investigated the capacity of M-CSF and other cytokines and hormones, alone or in combination, to induce bone resorption in explants of op/op metatarsals and metacarpals prelabeled with 45Ca. The effect on bone resorption was verified by counting the number of osteoclasts generated in the mineralized matrix. No osteoclast formation and no bone resorption were observed in the absence of M-CSF. M-CSF alone had only a slight effect at the high concentration of 10(4) units/ml. Addition of PTH or 1,25-(OH)2D3 together with M-CSF induced both osteoclastogenesis and bone resorption. The release of 45Ca was linear with time up to 15 days. PTH or 1,25-(OH)2D3 could not be substituted by TNF-alpha or IL-1, whereas IL-6 had a weak effect. M-CSF could not be replaced by GM-CSF. This study further emphasizes the role of M-CSF, PTH, and 1,25-(OH)2D3 in osteoclastogenesis.