OSGIN2 regulates osteogenesis of jawbone BMSCs in osteoporotic rats

Abstract

Background Augmentation of oxidative stress after estrogen deficiency leading to functional deficiency of jawbone bone marrow mesenchymal stem cells (BMSCs) causes jawbone loss in osteoporosis. OSGIN2, an oxidative stress induced factor, has been found to be associated with skeletal diseases. This study aims to investigate the function of OSGIN2 in jawbone BMSCs of osteoporotic rats. Jawbone BMSCs were used. Results Oxidative stress was increased in jawbone BMSCs of osteoporotic rats, meanwhile OSGIN2 was also up-regulated. Osteogenesis of jawbone BMSCs was declined under oxidative stress, while silence of OSGIN2 ameliorated the osteogenic deficiency. RORα and its downstream osteogenic markers (BSP and OCN) decreased under oxidative stress, while knocking-down of OSGIN2 restored their expressions. Inhibition of OSGIN2 improved the osteogenesis of jawbone BMSCs under oxidative stress, whereas down-regulation of RORα offset the effect. Intra-jawbone infusion of si-OSGIN2 rescued jawbone loss and promoted new bone deposition of osteoporotic rats. Conclusions Oxidative stress is redundant in osteoporosis, which results in up-regulation of OSGIN2. OSGIN2 restricts osteogenic ability of jawbone BMSCs via regulating RORα, while silencing of OSGIN2 rescues the osteogenic deficiency of osteoporotic rats.

The role of retinoic acid receptor-related orphan receptors in skeletal diseases

“…( 2) Oxidative stress: It has been reported that oxidative stress is a key trigger of osteoporosis. OSGIN2, an inducer of oxidative stress, prevented osteogenic differentiation of BMSCs by inhibiting RORa expression (24,25). ( 3) DNA methylation: Histone methylation has been recognized as an important modulator in the osteogenic differentiation of MSCs (26).…”