OPG Expression on Endothelial Cells and Modulation by IL-1B, PDGF, Insulin, and Glucose

Abstract

Introduction: Osteoprotegerin (OPG), an osteoclastogenesis inhibitor implicated in bone remodelling, has emerged as a potential biomarker for cardiovascular diseases. However, OPG circulating sources or the stimuli that increase its release and effects have not been established. Objective: The aim of the present study are to establish whether endothelial cells may be a potential source of OPG, different mediators and OPG effects on endothelial cells. Aim: The aim of the present study were: 1) to establish whether endothelial cells may be a potential source of circulating OPG, 2) to study induced OPG expression and release stimulated by different factors and 3) to explore proatherogenic effects of OPG on endothelial cells. Results: OPG protein and mRNA expression was highly and significantly increased by IL-1β, insulin and glucose. OPG secretion to the supernatant was increased by IL-1β (4758 ± 727 vs. 88 ± 33 pg/mL, p=0.001) and PDGF (451 ± 151 vs. 88 ± 33 pg/mL, p=0.009). Glucose and insulin did not elevate OPG concentration in the supernatant. Endothelial cells stimulated with OPG significantly increased the release of IL-6 to the supernatant (247 ± 60 vs. 148 ± 30, p=0.008) and IL-8 was also increased by OPG (1444 ± 70 vs. 1538 ± 28, p=0.09). Conclusion: Endothelial cells are a source of OPG in circulation and IL-1β, glucose and insulin stimulate its expression.