1. GPX7 Facilitates BMSCs Osteoblastogenesis via ER Stress and mTOR Pathway
- Author
-
Xiao-Yu Liu, Chenglin Wang, Fanzi Wu, Mengyu Liu, Ling Ye, Boer Li, Yu Shi, and Xuchen Hu
- Subjects
Male ,osteogenic differentiation ,Apoptosis ,medicine.disease_cause ,Mice ,Osteogenesis ,medicine ,Animals ,Humans ,Cells, Cultured ,PI3K/AKT/mTOR pathway ,chemistry.chemical_classification ,Glutathione Peroxidase ,Reactive oxygen species ,GPX7 ,TOR Serine-Threonine Kinases ,Endoplasmic reticulum ,Cell Cycle ,Mesenchymal stem cell ,Gene Expression Regulation, Developmental ,Cell Differentiation ,Mesenchymal Stem Cells ,Original Articles ,Cell Biology ,Alkaline Phosphatase ,Endoplasmic Reticulum Stress ,Immunohistochemistry ,Hedgehog signaling pathway ,Cell biology ,chemistry ,Adipogenesis ,Gene Knockdown Techniques ,Unfolded protein response ,Molecular Medicine ,Original Article ,BMSCs ,Reactive Oxygen Species ,ER stress ,Biomarkers ,Oxidative stress ,Signal Transduction - Abstract
Emerging evidence indicates extensive oxidative stress is a consequence of obesity which impairs bone formation. Glutathione peroxidase 7 (GPX7) is a conserved endoplasmic reticulum (ER) retention protein, lacking of which causes accumulation of reactive oxygen species (ROS) and promotes adipogenesis. Since the imbalance between osteogenic and adipogenic differentiation of bone marrow mesenchymal stem cell (BMSC) leads to severe bone diseases such as osteoporosis, it is critical to investigate the potential protective role of Gpx7 in osteogenesis. Here, we provide evidence that deficiency of Gpx7 reduces osteogenesis, but increases adipogenesis in both human BMSCs (hBMSCs) and mouse mesenchymal stem cell line. Interestingly, further studies indicate this defect can be alleviated by the ER stress antagonist, but not the ROS inhibitor, unveiling an unexpected finding that, unlike adipogenesis, lacking of Gpx7 inhibits osteogenesis mediating by induced ER stress instead of enhanced ROS. Furthermore, the mTOR signalling pathway is found down‐regulation during osteogenic differentiation in Gpx7‐deficient condition, which can be rescued by relief of ER stress. Taken together, for the first time we identify a novel function of Gpx7 in BMSCs’ osteogenic differentiation and indicate that Gpx7 may protect against osteoporotic deficits in humans through ER stress and mTOR pathway interplay.
- Published
- 2021