Low dose administration of macrophage colony-stimulating factor in mice

Macrophage-Colony Stimulating Factor (M-CSF) is critical for osteoclast differentiation and development. It has been previously observed that M-CSF administration and over-expression in mice causes an increase in cortical bone formation. We hypothesize that M-CSF increases osteoblast activity indirectly via coupling of these two bone cells. This study examined the impact on bone properties of relatively low doses of M-CSF in mice. Four groups of seven-week old C57BL/6J mice were used: (1) baseline controls, (2) placebo controls, (3) 10 micrograms/kg/day M-CSF, (4) 100 micrograms/kg/day M-CSF. Injections were administered daily for the 21-day study. Three bone labels of calcein and tetracycline were alternately administrated (days 0, 9 and 18) to allow quantification of new bone formation. MicroCT scans (15 micron resolution) were performed on the proximal end of the right tibiae (1.0 mm section of trabecular bone) and left femur mid-diaphysis (0.25 mm cortical section). Dry mass, mineral content and percent mineral composition were obtained from the left tibiae. Functional changes were not detected in the bones of the mice receiving low doses of M-CSF. In particular, as previous studies have reported in mice receiving high doses of M-CSF or transgenic mice overexpressing bone specific M-CSF, changes to cortical bone did not occur with the lower doses. This may indicate that high doses of M-CSF and/or longer periods of administration may be required to observe the anabolic effect of M-CSF on mouse cortical bone.