Role of osteoprotegerin and its ligands and competing receptors in atherosclerotic calcification.
Vascular calcification significantly impairs cardiovascular physiology, and its mechanism is under investigation. Many of the same factors that modulate bone osteogenesis, including cytokines, hormones, and lipids, also modulate vascular calcification, acting through many of the same transcription factors. In some cases, such as for lipids and cytokines, the net effect on calcification is positive in the artery wall and negative in bone. The mechanism for this reciprocal relation is not established. A recent series of reports points to the possibility that two bone regulatory factors, receptor activator of NF-kappaB ligand (RANKL) and its soluble decoy receptor, osteoprotegerin (OPG), govern vascular calcification and may explain the phenomenon. Both RANKL and OPG are widely accepted as the final common pathway for most factors and processes affecting bone resorption. Binding of RANKL to its cognate receptor RANK induces NF-kappaB signaling, which stimulates osteoclastic differentiation in preosteoclasts and induces bone morphogenetic protein (BMP-2) expression in chondrocytes. A role for RANKL and its receptors in vascular calcification is spported by several findings: a vascular calcification phenotype in mice genetically deficient in OPG; an increase in expression of RANKL, and a decrease in expression of OPG, in calcified arteries; clinical associations between coronary disease and serum OPG and RANKL levels; and RANKL induction of calcification and osteoblastic differentiation in valvular myofibroblasts.
Tintut
Yin
Y
Department of Medicine, University of California, Los Angeles, Los Angels, CA, USA.
Demer
Linda
L
D000818:Animals; D050197:Atherosclerosis / Q000209:etiology*; D002114:Calcinosis / Q000209:etiology*; D006801:Humans; D010012:Osteogenesis; D053244:Osteoprotegerin / Q000502:physiology*; D053245:RANK Ligand / Q000502:physiology*; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000502:physiology; D014652:Vascular Diseases / Q000209:etiology
D053244:Osteoprotegerin; D053245:RANK Ligand; D053221:TNF-Related Apoptosis-Inducing Ligand