HISTOLOGY AND HISTOPATHOLOGY

Cellular and Molecular Biology

 

Review

Canonical and non-canonical pathways of osteoclast formation

H.J. Knowles and N.A. Athanasou

Department of Pathology, Nuffield Orthopaedic Centre, University of Oxford, Oxford, UK.

Offprint requests to: Prof N.A. Athanasou, Department of Pathology, Nuffield Orthopaedic Centre, Windmill Road, Headington, Oxford, OX3 7LD, UK. e-mail: Nick.Athanasou@noc.anglox.nhs.uk


Summary. 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 NFκB 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, TNF
α 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. Histol Histopathol 24, 337-346 (2009)

Key words: Osteoclast, M-CSF, RANKL, resorption, osteolysis

DOI: 10.14670/HH-24.337