In particular we showed that: i) high Notch signaling in MM cells stimulates the release of the major osteoclastogenic soluble factor, RANKL; ii) MM cell-derived Notch ligands (Jagged1 and 2) activate Notch signaling in surrounding BMSCs, boosting the secretion of RANKL; iii) RANKL engages RANK on OCL progenitors, thereby activating the osteoclastogenic NF-kB pathway, which in turn stimulates the osteoclastogenic Notch signaling by promoting Notch2 expression; and iv) MM cell-derived Jagged ligands further boost Notch signaling in OCL progenitors by engaging Notch2. This evidence concerns the gene NOTCH2 and Miyoshi myopathy.