Figure 4.

Osteoimmunology: differentiation of osteoclast precursor into mature osteoclast. Synthesis of osteoblast, immune, and mesenchymal cell action in osteoclastogenesis: (1) T helper cells type 1 (Th1) that are playing a role in cellular immunity, are induced by IL-12, and secrete IL-2 and INF-γ (which has antiosteoclastogenic properties). (2) T helper cells type 2 (Th2) are involved in humoral immunity. They are induced by IL-4 and secrete IL-4 and IL-13. IL-4 has also antiosteoclastogenic properties. (3) The T helper cell type 17 (Th17) differentiates from naïve T CD4+ cells, has a proinflammatory role, and is implicated into autoimmune disease. Th17 is induced by TGF-β, IL-6, IL-21, and especially IL-23. Th17 cells secrete IL-17, IL-21, and IL-22. IL-17 is a major inflammatory cytokine and IL-21 stimulates Th17 differentiation and inhibits Th1 and Treg cells actions. In osteoclastogenesis, IL-17 can produce and induce RANKL expression by osteoblast, a situation that favors osteoresorption. This is not the only stimulatory activity of Th17 on osteoresorption as these cells express also higher levels of RANKL compared to Th1 and Th2. Finally, they also have higher levels of IL-1, IL-6, and TNF-α.