Direct and indirect effects of IL-17A on RANKL-Induced osteoclastogenesis

Inflammation-mediated bone loss is a major feature of various bone diseases, including chronic periodontitis, rheumatoid arthritis, and osteoarthritis, and is due to an imbalance in bone remodeling that favors resorption. This imbalance is caused by increased cytokine levels in the inflamed tissue. Interleukin (IL)-17 is secreted primarily by activated Th17 cells, and IL-17s and IL-17 receptors play an important role in many autoimmune and inflammatory diseases. The aim of this paper is to review the differences between the indirect effect of IL-17A via osteoblasts and the direct effect of IL-17A on differentiation of osteoclast precursors into osteoclasts and the function of mature osteoclasts in the presence of receptor activator of nuclear factor êâ ligand (RANKL). IL-17A stimulates the production of bone resorption-related inflammatory cytokines through an autocrine mechanism involving celecoxib-blocked prostaglandins (PGs), mainly PGE₂, in osteoblasts. Furthermore, IL-17A induces the differentiation of osteoclast precursors into osteoclasts and the function of mature osteoclasts via PGE₂ in osteoblasts. On direct effect of IL-17 to osteoclast precursors in the absence of RANKL, IL-17 induces the differentiation as well as indirect effect via osteoblasts. However, the differentiation and function of osteoclasts are suppressed by stimulating osteoclast precursors directly with IL-17A in the presence of RANKL. In conclusion, the effect of IL-17A on RANKL-induced osteoclastogenesis may conflict with the direct action on osteoclast precursors and the indirect action through osteoblasts.