Osteoprotegerin (OPG) and its ligand RANKL in vascular tissue

Abstract

Osteoprotegerin (OPG) is increased in arterial tissue from diabetic patients. OPG knock out mice develop vascular calcifications indicating that OPG is an inhibitor of the development of calcification. However, the observed calcifications may be secondary to osteoporosis in these animals. Furthermore, OPG neutralize the function of receptor activator of nuclear factor‐¿B ligand (RANKL).The project aim is to investigate direct functions of OPG and RANKL in vascular cells, including whether OPG is an inhibitor of the development of vascular calcification in vitro, without the interference of bone metabolism.OPG was knocked down in primary human vascular smooth muscle cells (HVSMCs) using siRNA. Microarray analysis was performed to investigate whether lack of OPG upregulates the expression of calcification‐associated genes. Pathway analysis (GenMAPP) showed no significant upregulation of the calcification‐associated gene group. Therefore, it was not possible to show that OPG is an inhibitor of calcification as suggested in animal studies.HVSMCs treated with OPG siRNA following stimulation with RANKL resulted in downregulation of the insulin signaling pathway (GenMAPP). The effect of RANKL on insulin signaling is a novel observation, which may provide an interesting putative link between the OPG‐RANKL balance and insulin signaling in diabetic patient.Research support: Novo Nordisk

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“…Functionally, OPG inhibits osteoclast differentiation and activity [ 52 ]. It interferes with interactions between receptor activators of nuclear factor kappa-Β ligand (RANKL) and RANK, which further inhibits osteoclast differentiation [ 53 ]. Shortly after its discovery, researchers used OPG as a probe for expression cloning and identified its ligand to be OPG-L/ODF [ 53 ].…”

“…It interferes with interactions between receptor activators of nuclear factor kappa-Β ligand (RANKL) and RANK, which further inhibits osteoclast differentiation [ 53 ]. Shortly after its discovery, researchers used OPG as a probe for expression cloning and identified its ligand to be OPG-L/ODF [ 53 ]. Moreover, RANKL and OPG-L/ODF have been established to be identical in terms of function [ 53 ].…”

“…Shortly after its discovery, researchers used OPG as a probe for expression cloning and identified its ligand to be OPG-L/ODF [ 53 ]. Moreover, RANKL and OPG-L/ODF have been established to be identical in terms of function [ 53 ]. Human RANKL is a polypeptide composed of 317 amino acids [ 54 ].…”