Mechanism of effect of IL-23 on human osteoclastogenesis. In a culture of human peripheral blood mononuclear cells, IL-23 directly induced osteoclastogenesis even in the absence of exogenous soluble receptor activator of NF-κB ligand (sRANKL). IL-17 induced by IL-23 from human activated T cells is the crucial cytokine for osteoclastogenesis through the mechanism of the RANK–RANKL system and TNF-α; IL-17 acts on monocytes, resulting in TNF-α production, inducing the differentiation of monocytes into osteoclasts by cooperating with RANKL, although RANKL alone expressed on monocytes does not induce osteoclastogenesis by binding to RANK. Furthermore, considering the inductive effect of IL-17 and the inhibitory effect of IFN-γ, it is speculated that the higher the ratio of IL-17 to IFN-γ, the greater the number of osteoclasts induced by IL-23. Ab, antibody; OPG, osteoprotegerin.