MACROPHAGE-COLONY-STIMULATING FACTOR RESTORES BONE-RESORPTION IN OP OP BONE IN-VITRO IN CONJUNCTION WITH PARATHYROID-HORMONE OR 1,25-DIHYDROXYVITAMIN D-3/

The in vivo administration of macrophage colony-stimulating factor (M- CSF) restores osteoclastogenesis and bone resorption in the op/op muri ne osteopetrosis. In vitro, exogenous M-CSF has been shown to be neces sary for the generation of osteoclast-like cells in cocultures of hema topoietic and mesenchymal cells obtained from this mutant. In this stu dy we investigated the capacity of M-CSF and other cytokines and hormo nes, alone or in combination, to induce bone resorption in explants of op/op metatarsals and metacarpals prelabeled with Ca-45. The effect o n bone resorption was verified by counting the number of osteoclasts g enerated in the mineralized matrix. No osteoclast formation and no bon e resorption were observed in the absence of M-CSF. M-CSF alone had on ly a slight effect at the high concentration of 10(4) units/ml. Additi on of PTH or 1,25-(OH)(2)D-3 together with M-CSF induced both osteocla stogenesis and bone resorption. The release of Ca-45 was linear with t ime up to 15 days. PTH or 1,25-(OH)(2)D-3 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, P TH, and 1,25-(OH)(2)D-3 in osteoclastogenesis.