title: Regulation of vascular calcification by osteoclast regulatory factors RANKL and osteoprotegerin.
abstract: Vascular calcification often occurs with advancing age, atherosclerosis, various metabolic disorders such as diabetes mellitus and end-stage renal disease, or in rare genetic diseases, leading to serious clinical consequences. Such mineralization can occur at various sites (cardiac valves, arterial intima or media, capillaries), involve localized or diffuse widespread calcification, and result from numerous causes that provoke active inflammatory and osteogenic processes or disordered mineral homeostasis. Although valuable research has defined many key factors and cell types involved, surprising new insights continue to arise that deepen our understanding and suggest novel research directions or strategies for clinical intervention in calcific vasculopathies. One emerging area in vascular biology involves the RANKL/RANK/OPG system, molecules of the tumor necrosis factor-related family recently discovered to be critical regulators of immune and skeletal biology. Evidence is accumulating that such signals may be expressed, regulated, and function in vascular physiology and pathology in unique ways to promote endothelial cell survival, angiogenesis, monocyte or endothelial cell recruitment, and smooth muscle cell osteogenesis and calcification. Concerted research efforts are greatly needed to understand these potential roles, clarify whether RANKL (receptor activator of nuclear factor kappaB ligand) promotes and osteoprotegerin (OPG) protects against vascular calcification, define how OPG genetic polymorphisms relate to cardiovascular disease, and learn whether elevated serum OPG levels reflect endothelial dysfunction in patients. Overall, the RANKL/RANK/OPG system may mediate important and complex links between the vascular, skeletal, and immune systems. Thus, these molecules may play a central role in regulating the development of vascular calcification coincident with declines in skeletal mineralization with age, osteoporosis, or disease.
authors.affiliation: Department of Biology and Division of Bone and Mineral Research, Washington University, St Louis, Mo 63130, USA. collin@biology.wustl.edu
authors.forename: Patricia
authors.initials: P
authors.lastname: Collin-Osdoby
mesh_terms: D000818:Animals; D001161:Arteriosclerosis / Q000503:physiopathology; D001842:Bone and Bones / Q000502:physiology; D002114:Calcinosis / Q000150:complications / Q000503:physiopathology*; D002352:Carrier Proteins / Q000494:pharmacology / Q000502:physiology*; D004730:Endothelium, Vascular / Q000187:drug effects; D006023:Glycoproteins / Q000494:pharmacology / Q000502:physiology*; D006801:Humans; D007107:Immune System / Q000502:physiology; D008562:Membrane Glycoproteins / Q000494:pharmacology / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D010010:Osteoclasts / Q000502:physiology*; D010024:Osteoporosis / Q000150:complications / Q000503:physiopathology; D053244:Osteoprotegerin; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D018160:Receptors, Cytoplasmic and Nuclear / Q000502:physiology*; D018124:Receptors, Tumor Necrosis Factor; D014652:Vascular Diseases / Q000150:complications / Q000503:physiopathology*
chemical_list: D002352:Carrier Proteins; D006023:Glycoproteins; D008562:Membrane Glycoproteins; D053244:Osteoprotegerin; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D018160:Receptors, Cytoplasmic and Nuclear; D018124:Receptors, Tumor Necrosis Factor; C505686:TNFRSF11A protein, human; C506030:TNFRSF11B protein, human; C505688:TNFSF11 protein, human; C505687:Tnfrsf11a protein, mouse; C506031:Tnfrsf11b protein, mouse; C505689:Tnfsf11 protein, mouse