M-CSF accelerates orthodontic tooth movement by targeting preosteoclasts in mice

Abstract Objective: To test the use of macrophage colony-stimulating factor (M-CSF), an early osteoclast recruitment/differentiation factor, in increasing the rate of osteoclastic recruitment and differentiation as a means of accelerating tooth movement. Materials and Methods: The distribution of osteoclasts and their precursors in the periodontal ligament (PDL) of teeth was initially characterized in a mouse model by immunohistochemical expression analyses of markers of osteoclast differentiation. We next administered two different dosages of M-CSF in the PDL of molars subject to force. Tooth movement was measured and correlated with changes in expression of M-CSF downstream genes in the PDL. Results: We found that monocytes may have differentiated into preosteoclasts before being recruited to the PDL during the lag phase of tooth movement, and an influx of multinucleated osteoclasts occurred after 6 days. The lower dose of M-CSF was found to be most effective in increasing the amount of tooth movement a...