Effect of intermittent hypoxia on osteoprotegerin expression in rat liver

Abstract

Hypoxia is one of the most frequently encountered stress factors in both health and disease. Intermittent hypoxia (IH) is the most common pattern of hypoxic exposure. Osteoprotegerin (OPG) is produced by various cell types, including hepatocytes. Alterations in serum and tissue levels of OPG have been linked to many types of diseases, and clinical significance of OPG expression status has recently been clarified. However, the effect of IH on the expression of OPG in the liver remains unknown. The aim of this study was to investigate the effect of IH on hepatic OPG expression. Male Sprague-Dawley rats were placed in a hypobaric chamber (282 mm Hg, 30 min/d, 14 d). Hepatic OPG mRNA and protein levels were determined using quantitative real-time RT-PCR and immunohistochemical staining, respectively. A significant decline in hepatic OPG expression at both mRNA and protein levels was reported in the IH model. In hypoxic rats, IH significantly decreased the OPG mRNA expression, when compared with the normoxic control (P=0.001). Immunohistochemistry revealed that the normoxic livers exhibited a moderate to strong, homogeneous cytoplasmic staining of hepatocytes. In contrast, all the hypoxic livers showed a significantly reduced OPG staining intensity, when compared with the normoxic livers. In 9 of the 12 (75.0%) hypoxic rats, hepatic OPG immunoreactivity was undetectable. Our preliminary data suggest that IH exposure downregulates hepatic OPG at both the transcriptional and translational levels. Further investigations are necessary to clarify the mechanism by which hypoxia would induce OPG downregulation.