FIG. 1. Osteoclast differentiation is stimulated by M-CSF and RANKL. M-CSF induces the proliferation and survival of osteoclast precursor cells through activation of ERK and Akt. RANKL recruits TRAF6 to activate MAPKs, Akt, and NFATc1 to promote differentiation of osteoclast precursors to osteoclasts. In addition to RANKL signaling, costimulatory signaling provides robust NFATc1 induction through activation of calcium signaling.
