Multiple myeloma cells directly stimulate bone resorption in vitro by down-regulating mature osteoclast apoptosis

Multiple myeloma (MM) is characterized by devastating bone destruction mainly due to stimulation of osteoclastogenesis. However, whether MM cells can directly influence osteoclast apoptosis, a mechanism that would contribute to increase the number of active osteoclasts, has not been addressed yet. Herein, using authentic mature rabbit osteoclasts, we demonstrated that conditioned media (CM) prepared from U266 and RPMI8226 cells but not from LP-1 and OPM-2 cells, stimulated bone resorption and inhibited osteoclast apoptosis in a dose-dependent manner. The MM cells which exerted an anti-apoptotic effect secreted high amounts of M-CSF and addition of a neutralizing antibody against M-CSF reversed the CM effects. Imatinib mesylate, a tyrosine kinase inhibitor that can target the M-CSF receptor, also prevented the effect of CM. These findings suggest that M-CSF originating from MM cells may play a critical role in MM bone disease by decreasing osteoclast apoptosis.