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

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.

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.

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 and expression of M-CSF downstream genes and TRAP, an osteoclast marker. In contrast, administration of a higher dose of M-CSF resulted in a decrease in the expression of one gene downstream of M-CSF and possible inhibition of osteoclast formation.

Exogenous administration of optimal dosages of M-CSF to orthodontically moved teeth provides potential for clinical studies in accelerating tooth movement.