Establishment of OPG Transgenic Mice and the Effect of OPG on Bone Microarchitecture.

Ying Wu,Hui Guo,Qiong Luo,Ziying Yu,Xuyu Zu,Jianghua Liu,Eryuan Liao

doi:10.1155/2013/125932

Abstract

Osteoprotegerin (OPG) plays a determinant role in regulating bone metabolism, but the effect of OPG on bone microarchitecture needs to be further elucidated. We attempted to construct pCI-hOPGp-mOPG vector containing human OPG promoter and FLAG tag and to microinject vector into fertilized zygotes from C57BL/6J × CBA mice to prepare transgenic mice. The OPG transgenic positive mice were identified by PCR and western blotting. Twelve-week-old OPG transgenic mice (OPG-Tg mice) and wild-type mice (WT mice) were utilized in the study of bone microarchitecture. Microcomputed tomography (micro-CT) data showed that compared with WT mice, the tibia of OPG-Tg mice showed an increased volumetric BMD (vBMD), tissue BMD (tBMD), trabecular thickness (Tb.Th), and trabecular number (Tb.N), and a decreased trabecular separation (Th.Sp) (P < 0.05) . The cortical bone microarchitecture parameters, such as cortical area (Ct.Ar), cortical thickness (Ct.Th), cortical BMD (Ct.BMD), cortical BMC (Ct.BMC), BMD, and BMC of femur, were increased, and the inner perimeter (In.Pm) was decreased, in OPG-Tg mice, compared to those in WT mice (P < 0.05). The established OPG transgenic mouse model could be valuable for further studying the biological significance and gene regulation of OPG in vivo.

Highlights

The skeleton is in a dynamic state, being continually degraded and renewed in a tightly regulated remodeling process that involves a complex network of systemic hormones and local factors
OPG, a secreted member of the tumor necrosis factor receptor superfamily, has been identified as an osteoblast-derived regulator of bone resorption and bone mass, and it is implicated in the pathogens of postmenopausal osteoporosis and other metabolic bone diseases
OPG acts by neutralizing RANKL, an essential cytokine required for osteoclast formation and activation [1]

Summary

Introduction

The skeleton is in a dynamic state, being continually degraded and renewed in a tightly regulated remodeling process that involves a complex network of systemic hormones and local factors. OPG, a secreted member of the tumor necrosis factor receptor superfamily, has been identified as an osteoblast-derived regulator of bone resorption and bone mass, and it is implicated in the pathogens of postmenopausal osteoporosis and other metabolic bone diseases. Recombinant OPG can be used for postmenopausal women for the treatment of osteoporosis [8]. These data suggested that OPG could act as a key factor in the regulation of bone mass and implied a utility for OPG in the treatment of metabolic bone disease. A suitable animal model with OPG overexpression is needed for the further insight into the implication of OPG in metabolic bone disease

Methods

Results

Conclusion