The Alternative Faces of Macrophage Generate Osteoclasts

Figure 4

Effect of cytokines on the generation of osteoclasts. TNF- promotes osteoclastogenesis directly, increasing the number of osteoclasts, and indirectly, increasing RANKL production by osteoblasts. The exposition of preosteoclast to TNF- before RANKL inhibits osteoclastogenesis. IL-6 promotes osteoclast differentiation in the presence of osteoblasts and can synergize with TNF- to induce osteoclastogenesis. On the contrary, it directly inhibits the differentiation of preosteoclast promoting the production of M1-like macrophage markers. IL-34 is produced by osteoblasts and recognizes the receptor for M-CSF (c-fms), thus promoting osteoclasts differentiation. IL-33 inhibits osteoclastogenesis addressing the preosteoclast versus M2-like macrophage differentiation. IL-10 is a potent anti-inflammatory cytokine produced mainly by M2 macrophages, which prevent the differentiation of osteoclast progenitors in preosteoclast. IL-4 promotes the M2 phenotype and inhibits the RANKL-induced osteoclast differentiation.