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- Title
Selenium-modified bone cement promotes osteoporotic bone defect repair in ovariectomized rats by restoring GPx1-mediated mitochondrial antioxidant functions.
- Authors
Zhou, Quan; Chen, Weikai; Gu, Chao; Liu, Hao; Hu, Xiayu; Deng, Lei; He, Wei; Xu, Yong; Zhu, Xuesong; Yang, Huilin; Chen, Xi; He, Fan; Liu, Tao
- Abstract
Over-accumulation of reactive oxygen species (ROS) causes mitochondrial dysfunction and impairs the osteogenic potential of bone marrow-derived mesenchymal stem cells (BMMSCs). Selenium (Se) protects BMMSCs from oxidative stress-induced damage; however, it is unknown whether Se supplementation can promote the repair of osteoporotic bone defects by rescuing the impaired osteogenic potential of osteoporotic BMMSCs (OP-BMMSCs). In vitro treatment with sodium selenite (Na2SeO3) successfully improved the osteogenic differentiation of OP-BMMSCs, as demonstrated by increased matrix mineralization and up-regulated osteogenic genes expression. More importantly, Na2SeO3 restored the impaired mitochondrial functions of OP-BMMSCs, significantly up-regulated glutathione peroxidase 1 (GPx1) expression and attenuated the intracellular ROS and mitochondrial superoxide. Silencing of Gpx1 completely abrogated the protective effects of Na2SeO3 on mitochondrial functions of OP-BMMSCs, suggesting the important role of GPx1 in protecting OP-BMMSCs from oxidative stress. We further fabricated Se-modified bone cement based on silk fibroin and calcium phosphate cement (SF/CPC). After 8 weeks of implantation, Se-modified bone cement significantly promoted bone defect repair, evidenced by the increased new bone tissue formation and enhanced GPx1 expression in ovariectomized rats. These findings revealed that Se supplementation rescued mitochondrial functions of OP-BMMSCs through activation of the GPx1-mediated antioxidant pathway, and more importantly, supplementation with Se in SF/CPC accelerated bone regeneration in ovariectomized rats, representing a novel strategy for treating osteoporotic bone fractures or defects.
- Subjects
SELENIUM; MITOCHONDRIA; OSTEOPOROSIS; SUPEROXIDES; MESENCHYMAL stem cells; BONE growth; REACTIVE oxygen species; BONE cements
- Publication
Regenerative Biomaterials, 2023, Vol 10, p1
- ISSN
2056-3418
- Publication type
Article
- DOI
10.1093/rb/rbad011