IL-6, RANKL, TNF-alpha/IL-1: interrelations in bone resorption pathophysiology.
All osteogenic cells (osteoclasts, osteoblasts) contribute individually to bone remodeling. Their cellular interactions control their cellular activities and the bone remodeling intensity. These interactions can be established either through a cell-cell contact, involving molecules of the integrin family, or by the release of many polypeptidic factors and/or their soluble receptor chains. These factors can act directly on osteogenic cells and their precursors to control differentiation, formation and functions (matrix formation, mineralization, resorption...). Here, we present the involvement of three groups of cytokines which seem to be of particular importance in bone physiology: interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha) (TNF-alpha)/IL-1, and the more recently known triad osteoprotegerin (OPG)/receptor activator of NF-kappaB (RANK)/RANK ligand (RANKL). The interactions between these three groups are presented within the framework of bone resorption pathophysiology such as tumor associated osteolysis. The central role of the OPG/RANK/RANKL triad is pointed out.
Kwan Tat
Steeve
S
Laboratoire de Physiopathologie de la Résorption Osseuse et Thérapie des Tumeurs Osseuses Primitives, Faculté de Médecine, 1 rue Gaston Veil, BP 53508, 44035 Nantes 1, France.
Padrines
Marc
M
Théoleyre
Sandrine
S
Heymann
Dominique
D
Fortun
Yannick
Y
D000818:Animals; D017209:Apoptosis; D001862:Bone Resorption; D002352:Carrier Proteins / Q000502:physiology*; D002450:Cell Communication; D002454:Cell Differentiation; D006801:Humans; D016023:Integrins / Q000378:metabolism; D007375:Interleukin-1 / Q000502:physiology*; D015850:Interleukin-6 / Q000502:physiology*; D008562:Membrane Glycoproteins / Q000502:physiology*; D008954:Models, Biological; D010006:Osteoblasts / Q000502:physiology; D010010:Osteoclasts / Q000502:physiology; D011485:Protein Binding; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*
D002352:Carrier Proteins; D016023:Integrins; D007375:Interleukin-1; D015850:Interleukin-6; D008562:Membrane Glycoproteins; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; C505686:TNFRSF11A protein, human; C505688:TNFSF11 protein, human; D014409:Tumor Necrosis Factor-alpha