FIGURE 4.

Osteoclastogenesis regulated by osteoblasts. TLR4 plays a key role in the cell fate of bone marrow monocytes (BMMs). During the first stage of commitment, TLR4 activation alone, promotes the conversion of these precursor cells into macrophages, and blocks osteoclastogenesis. However, osteoblasts can shift this fate to the formation of osteoclasts. TLR4 activation of osteoblasts induces the production of receptor activator of nuclear factor kappa-B ligand (RANKL) and macrophage-colony stimulating factors (M-CSF). The presence of these factors during the commitment phase prevents the macrophage fate and drives to osteoclast formation. Instead during the development stage, TLR4 activation triggers both cell fates. Thus, osteoclasts formation mediated by TLR4 depends on the presence or absence of osteoblast-derived RANKL during the commitment stage.