NOTCH signaling is a key regulator of cell fate decisions in prenatal skeletal development
and is active during adult tissue renewal. In addition, its association with neoplasia suggests
that it is a candidate therapeutic target. We find that attenuated NOTCH signaling enhances
osteoclastogenesis and bone resorption in vitro and in vivo by a combination of molecular
mechanisms. First, deletion of Notch1-3 in bone marrow macrophages directly promotes
their commitment to the osteoclast phenotype. These osteoclast precursors proliferate more …