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Figure 3. Several cytokines and inflammatory mediators have been shown to be able to stimulate osteoclast formation and bone resorption, and have therefore been implicated in the pathogenesis of inflammation-induced bone resorption. Some of the cytokines, the two kinins bradykinin and kallidin, as well as thrombin, are stimulatory, whereas other cytokines are inhibitory. The stimulatory cytokines exert their effects not by affecting the osteoclast progenitor cells directly, but by stimulating the RANKL/OPG ratio in periosteal osteoblasts. The inhibitory cytokines cause their effects either indirectly, by affecting osteoblasts, or, in some cases, directly, by affecting the osteoclast progenitor cells. Chemokines are important for the recruitment of osteoclast progenitor cells to the inflammatory site and also for the fusion of these cells to multi-nucleated osteoclasts.
