Selenium-modified bone cement promotes osteoporotic bone defect repair in ovariectomized rats by restoring GPx1-mediated mitochondrial antioxidant functions  

作　　者：Quan Zhou Weikai Chen Chao Gu Hao Liu Xiayu Hu Lei Deng Wei He Yong Xu Xuesong Zhu Huilin Yang Xi Chen Fan He Tao Liu 

机构地区：[1]Department of Orthopaedics,The First Affiliated Hospital of Soochow University,Suzhou 215006,China [2]Orthopaedic Institute,Medical College,Soochow University,Suzhou 215007,China [3]Department of Orthopaedics,Suzhou Dushu Lake Hospital,Suzhou 215125,China [4]Department of Pathology,The Third Affiliated Hospital of Soochow University,Changzhou 213003,China

出　　处：《Regenerative Biomaterials》2023年第1期533-548,共16页再生生物材料（英文版）

基　　金：supported by the National Natural Science Foundation of China(82072476,82072410);Natural Science Foundation of Jiangsu Province(BK20220046);Major Science and Technology Project of Changzhou Health Commission(ZD202001);the Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD);Key Laboratory of Orthopaedics of Suzhou(SZS2022017).

摘　　要：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(Na_(2)SeO_(3))successfully improved the osteogenic differentiation of OP-BMMSCs,as demonstrated by increased matrix mineralization and up-regulated osteogenic genes expression.More importantly,Na_(2)SeO_(3) 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 Na_(2)SeO_(3) 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.

关 键 词：sodium selenite OSTEOPOROSIS GPx1 mitochondrial function bone cement 

分 类 号：R318.08[医药卫生—生物医学工程]