title: The Alternative Faces of Macrophage Generate Osteoclasts.
abstract: The understanding of how osteoclasts are generated and whether they can be altered by inflammatory stimuli is a topic of particular interest for osteoclastogenesis. It is known that the monocyte/macrophage lineage gives rise to osteoclasts (OCs) by the action of macrophage colony stimulating factor (M-CSF) and receptor activator of nuclear factor-kB ligand (RANKL), which induce cell differentiation through their receptors, c-fms and RANK, respectively. The multinucleated giant cells (MGCs) generated by the engagement of RANK/RANKL are typical OCs. Nevertheless, very few studies have addressed the question of which subset of macrophages generates OCs. Indeed, two main subsets of macrophages are postulated, the inflammatory or classically activated type (M1) and the anti-inflammatory or alternatively activated type (M2). It has been proposed that macrophages can be polarized in vitro towards a predominantly M1 or M2 phenotype with the addition of granulocyte macrophage- (GM-) CSF or M-CSF, respectively. Various inflammatory stimuli known to induce macrophage polarization, such as LPS or TNF-α, can alter the type of MGC obtained from RANKL-induced differentiation. This review aims to highlight the role of immune-related stimuli and factors in inducing macrophages towards the osteoclastogenesis choice.
authors.affiliation: Institute of Biomedicine and Molecular Immunology "Alberto Monroy", National Research Council, Via Ugo La Malfa 153, 90146 Palermo, Italy.
authors.forename: N
authors.initials: N
authors.lastname: Lampiasi
authors.affiliation: Institute of Biomedicine and Molecular Immunology "Alberto Monroy", National Research Council, Via Ugo La Malfa 153, 90146 Palermo, Italy.
authors.forename: R
authors.identifier: 0000-0001-8683-8872
authors.initials: R
authors.lastname: Russo
authors.affiliation: Institute of Biomedicine and Molecular Immunology "Alberto Monroy", National Research Council, Via Ugo La Malfa 153, 90146 Palermo, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Zito
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology; D016173:Macrophage Colony-Stimulating Factor / Q000378:metabolism*; D010010:Osteoclasts / Q000166:cytology / Q000378:metabolism*; D053245:RANK Ligand / Q000378:metabolism*; D053246:Receptor Activator of Nuclear Factor-kappa B / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D008070:Lipopolysaccharides; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; C505686:TNFRSF11A protein, human; C505688:TNFSF11 protein, human; D014409:Tumor Necrosis Factor-alpha; D016173:Macrophage Colony-Stimulating Factor