Our study elucidates a molecular mechanism for the osteocyte-myeloma interaction, in which myeloma cell TP/2DDR upregulates CIITA expression in osteocytes; the increased CIITA enhances histone acetylation of TNFSF11 and SOST genes; and promotes RANKL and sclerostin secretion from osteocytes. The gene discussed is TNFSF11; the disease is plasma cell myeloma.