Effect of macrophage colony-stimulating factor receptor c-Fms antibody on lipopolysaccharide-induced pathological osteoclastogenesis and bone resorption

Abstract

Lipopolysaccharide (LPS) is a major component of Gram-negative bacteria cell walls and is a well-known potent inducer of inflammation and pathogens of inflammatory bone loss. Formation of osteoclasts is highly dependent on the presence of macrophage colony-stimulating factor (M-CSF) and receptor activator of nuclear factor kappa-B ligand (RANKL). Recent reports indicate that biological preparations, including anti-RANKL antibody and anti-tumor necrosis factor-β? antibody, positively influence rheumatoid arthritis and osteoporosis. In this study, we aimed to investigate whether the M-CSF receptor c-Fms antibody would inhibit the formation of osteoclasts. C57BL6/J mice were injected with either LPS, LPS and anti-c-Fms antibody, anti-c-Fms antibody, or PBS into the supracalvariae. Animals were sacrificed and calvariae fixation and demineralization were performed. Histological sections of calvariae were stained for tartrate-resistant acid phosphatase (TRAP). In mice administered with both LPS and the anti-c-Fms antibody, osteoclast numbers were lower than those in mice administered with LPS alone. Moreover, levels of TRACP-5b, a bone resorption marker in mice serum, were lower in mice administered with both LPS and the anti-c-Fms antibody than in mice administered with LPS alone. These results suggest that M-CSF and its receptor are potential therapeutic targets in LPS-induced osteoclastogenesis, and that the anti-c-Fms antibody might be useful for inhibition of inflammation-induced bone erosion. In this study, we describe and discuss the effect the anti-c-Fms antibody has on pathological osteoclastogenesis and bone resorption.