Review

Cellular and Molecular Life Sciences

, Volume 64, Issue 18, pp 2334-2350

First online:

RANKL, RANK, osteoprotegerin: key partners of osteoimmunology and vascular diseases

  • M. Baud’huinAffiliated withLaboratoire de Physiopathologie de la Résorption Osseuse et Thérapie des Tumeurs Osseuses Primitives, EA3822, Université de Nantes, Nantes Atlantique UniversitésINSERM, ERI 7
  • , F. LamoureuxAffiliated withLaboratoire de Physiopathologie de la Résorption Osseuse et Thérapie des Tumeurs Osseuses Primitives, EA3822, Université de Nantes, Nantes Atlantique UniversitésINSERM, ERI 7
  • , L. DuplombAffiliated withLaboratoire de Physiopathologie de la Résorption Osseuse et Thérapie des Tumeurs Osseuses Primitives, EA3822, Université de Nantes, Nantes Atlantique UniversitésINSERM, ERI 7
  • , F. RédiniAffiliated withLaboratoire de Physiopathologie de la Résorption Osseuse et Thérapie des Tumeurs Osseuses Primitives, EA3822, Université de Nantes, Nantes Atlantique UniversitésINSERM, ERI 7
  • , D. HeymannAffiliated withLaboratoire de Physiopathologie de la Résorption Osseuse et Thérapie des Tumeurs Osseuses Primitives, EA3822, Université de Nantes, Nantes Atlantique UniversitésINSERM, ERI 7CHU de Nantes Email author 

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Abstract.

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.

Keywords.

RANKL osteoprotegerin bone remodeling osteoclast osteolysis osteoimmunology cardiovascular disease