Canonical and non-canonical pathways of osteoclast formation.
Physiological and pathological bone resorption is mediated by osteoclasts, multinucleated cells which are formed by the fusion of monocyte / macrophage precursors. The canonical pathway of osteoclast formation requires the presence of the receptor activator for NFkappaB ligand (RANKL) and macrophage colony stimulating factor (M-CSF). Non-canonical pathways of osteoclast formation have been described in which cytokines / growth factors can substitute for RANKL or M-CSF to induce osteoclast formation. Substitutes for RANKL include LIGHT, TNFalpha and interleukins 6, 11 and 8. M-CSF substitutes include vascular endothelial growth factor (VEGF), placental growth factor (PlGF), FLt-3 ligand and hepatocyte growth factor (HGF). These growth factors can also influence canonical (RANKL / M-CSF-induced) osteoclast formation. Both canonical and non-canonical pathways of osteoclast formation play a role in the formation of osteolytic lesions where there is increased osteoclast formation and activity, such as in giant cell tumour of bone.
Knowles
H J
HJ
Department of Pathology, Nuffield Orthopaedic Centre, University of Oxford, Oxford, UK.
Athanasou
N A
NA
D016207:Cytokines / Q000378:metabolism; D006801:Humans; D016173:Macrophage Colony-Stimulating Factor / Q000378:metabolism / Q000502:physiology; D008954:Models, Biological; D010010:Osteoclasts / Q000378:metabolism* / Q000473:pathology* / Q000502:physiology*; D010014:Osteolysis; D053245:RANK Ligand / Q000378:metabolism; D053246:Receptor Activator of Nuclear Factor-kappa B / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D016207:Cytokines; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D014409:Tumor Necrosis Factor-alpha; D016173:Macrophage Colony-Stimulating Factor