Differential activity of granulocyte-macrophage and macrophage colony stimulating factors on bone resorption in fetal rat long bone organ cultures

In this study, the ability of recombinant human macrophage (M) and murine granulocyte-macrophage macrophage (GM) colony stimulating factor (CSF) to affect both basal and stimulated bone resorption in fetal rat long-bone organ cultures was assessed. It was found that M-CSF does not affect basal bone resorption or bone resorption stimulated by parathyroid hormone, recombinant human interleukin 1β, prostaglandin E 2 (PGE 2), and 1,25 dihydroxy vitamin D 3. Specifically, M-CSF at concentrations as high as 30 nM (1 μg/mL) did not modulate 45Ca release from fetal rat long bones stimulated by these agents. The addition of recombinant murine GM-CSF (at equal molar concentration to M-CSF) also did not affect bone resorption stimulated by parathyroid hormone and interleukin 1β. On the other hand, GM-CSF stimulated basal bone resorption over a 120-h period and augmented the resorption mediated by exogenous PGE 2 over a 48-h incubation. In addition, GM-CSF was shown to stimulate production of endogenous PGE 2 in cultures of bone rudiments. These effects on bone resorption were blocked by the addition of prostaglandin synthesis inhibitors and specific antibodies to murine GM-CSF. These data indicate that M-CSF does not act as a regulator of bone turnover, but GM-CSF may cause bone resorption by stimulating the synthesis of PGE 2 in bone.