RANKL, RANK, osteoprotegerin: key partners of osteoimmunology and vascular diseases.
1997 saw the identification of a novel set of proteins within the tumor necrosis factor (TNF)/TNF receptor families that are required for the control of bone remodeling. Therefore, these receptors, receptor activator of nuclear factor kappa B (RANK), osteoprotegerin (OPG) and their ligand RANK ligand (RANKL) became the critical molecular triad controlling osteoclastogenesis and pathophysiologic bone remodeling. However, the establishment of the corresponding knock-out and transgenic mice revealed unexpected results, most particularly, the involvement of these factors in the vascular system and immunity. Thus, the OPG/RANK/RANKL molecular triad appears to be associated with vascular calcifications and plays a pivotal function in the development of the immune system through dendritic cells. OPG/RANK/RANKL thus constitute a molecular bridge spanning bone metabolism, vascular biology and immunity. This review summarizes recent knowledge of OPG/RANK/RANKL interactions and activities as well as the current evidence for their participation in osteoimmunology and vascular diseases. In fine, the targeting of the OPG/RANK/RANKL axis as novel therapeutic approaches will be discussed.
Baud'huin
M
M
Laboratoire de Physiopathologie de la Résorption Osseuse et Thérapie des Tumeurs Osseuses Primitives, EA3822, Université de Nantes, Nantes Atlantique Universités, F-44035, Nantes, France.
Lamoureux
F
F
Duplomb
L
L
Rédini
F
F
Heymann
D
D
D000818:Animals; D001842:Bone and Bones / Q000166:cytology / Q000276:immunology*; D006801:Humans; D051379:Mice; D053244:Osteoprotegerin / Q000737:chemistry / Q000378:metabolism*; D053245:RANK Ligand / Q000737:chemistry / Q000378:metabolism*; D053246:Receptor Activator of Nuclear Factor-kappa B / Q000737:chemistry / Q000378:metabolism*; D014652:Vascular Diseases / Q000378:metabolism*
D053244:Osteoprotegerin; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B