IL-1β, TNF-α, and IL-6 have also been shown to stimulate osteoclast differentiation and bone resorption in a synergistic manner (35), and perhaps unexpectedly, to increase the production of both RANKL and OPG in the human osteosarcoma cell line MG-63 (36–38), although the dominant outcome was a net increase in RANKL activity (39, 40). The gene discussed is TNF; the disease is osteosarcoma.