We explored whether P2X7 receptor has consequences for the myeloma–bone interaction using a co-culture assay to assess four conditions: RPMI-8226 (1) treated with 300 μM BzATP for 90 min, with or without a 30 min antagonist pretreatment (HMCL), (2) treated and then co-cultured with mature primary osteoblasts (HMCL+OB), (3) treated and then co-cultured with resorbing osteoclasts (HMCL+OC), and (4) treated and then co-cultured with both bone cells (HMCL + OB + OC). Here, P2RX7 is linked to plasma cell myeloma.