Anti-c-Fms antibody inhibits lipopolysaccharide-induced osteoclastogenesis in vivo.

It has been reported that lipopolysaccharide (LPS) has the ability to induce inflammation and osteoclastogenesis. Osteoclast formation is dependent on macrophage-colony-stimulating factor (M-CSF) and ligand for the receptor activator of necrosis factor-kB. In this study, the effect of antibody against c-Fms, which is the receptor of M-CSF, on LPS-mediated osteoclastogenesis was investigated in mice. LPS was administered with or without anti-c-Fms antibody into the supracalvaria of mice. The number of osteoclasts and the levels of mRNA for cathepsin K and tartrate-resistant acid phosphatase, which are osteoclast markers, in mice administered both LPS and anti-c-Fms antibody were lower than those in mice administered LPS alone. The level of tartrate-resistant acid phosphatase 5b as a marker of bone resorption in mice administered both LPS and anti-c-Fms antibody was also lower. Furthermore, the expression of the receptor activator of necrosis factor-kB, which is receptor activator of nuclear factor kappa-B ligand, was increased upon LPS administration, but the expression was inhibited by anti-c-Fms antibody. These results showed that anti-c-Fms antibody inhibits LPS-induced osteoclast formation. In conclusion, M-CSF and its receptor are potential therapeutic targets in bacterial infection-induced osteoclastogenesis, and anti-c-Fms antibody might be useful for inhibition of bacterial infection-induced bone destruction.