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 s...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.展开更多
Bone necrosis after injecting of polymethylmethacrylate(PMMA)bone cement will lead to re-fracture of bone tissue.As a new type of necrosis,there is little research related to the necroptosis of surrounding bone tissue...Bone necrosis after injecting of polymethylmethacrylate(PMMA)bone cement will lead to re-fracture of bone tissue.As a new type of necrosis,there is little research related to the necroptosis of surrounding bone tissue near the bone cement.The purpose of our study was to(i)investigate the presence of necroptosis in vivo and,(ii)established as a new type of bone cement containing PMMA,calcium phosphate cement(CPC)and Necrostatin-1(Nec-1)to inhibit necroptosis of bone tissue.A total of 12 Japanese rabbits were used to establish the animal model and randomly divided into 4 groups signed as a control group,PMMA group,PMMA–CPC group and PMMA–CPC–Nec-1 group,respectively.We used scanning electron microscope to observe the structure of the samples,used HE staining to detect the necrosis,and used western blotting as well as ELISA test to examine the iconic molecule receptor interacting protein kinase-3(RIP 3)protein and tumor necrosis factor a(TNF-a).After analyzing the results of our study,we found that the structure in both PMMA bone cement group and composite bone cement group was damaged and there was an evidence of necrosis,but it was absent in control group.Through molecule detection,the RIP 3 protein expression was decreased in PMMA–CPC–Nec-1(P<0.05).TNF-a expression was increased in bone cement groups with and without CPC(P<0.05),but was inhibited in PMMA–CPC–Nec-1 group.We have concluded that the necroptosis could be confirmed in bone tissue necrosis induced by TNF-a after bone cement injection and also could be inhibited by composite bone cement with Nec-1.展开更多
基金supported by the National Natural Science Foundation of China(82072476,82072410)Natural Science Foundation of Jiangsu Province(BK20220046)+2 种基金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).
文摘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.
基金supported by the National Nature Science Foundation of China(NNSFC No.81472086).
文摘Bone necrosis after injecting of polymethylmethacrylate(PMMA)bone cement will lead to re-fracture of bone tissue.As a new type of necrosis,there is little research related to the necroptosis of surrounding bone tissue near the bone cement.The purpose of our study was to(i)investigate the presence of necroptosis in vivo and,(ii)established as a new type of bone cement containing PMMA,calcium phosphate cement(CPC)and Necrostatin-1(Nec-1)to inhibit necroptosis of bone tissue.A total of 12 Japanese rabbits were used to establish the animal model and randomly divided into 4 groups signed as a control group,PMMA group,PMMA–CPC group and PMMA–CPC–Nec-1 group,respectively.We used scanning electron microscope to observe the structure of the samples,used HE staining to detect the necrosis,and used western blotting as well as ELISA test to examine the iconic molecule receptor interacting protein kinase-3(RIP 3)protein and tumor necrosis factor a(TNF-a).After analyzing the results of our study,we found that the structure in both PMMA bone cement group and composite bone cement group was damaged and there was an evidence of necrosis,but it was absent in control group.Through molecule detection,the RIP 3 protein expression was decreased in PMMA–CPC–Nec-1(P<0.05).TNF-a expression was increased in bone cement groups with and without CPC(P<0.05),but was inhibited in PMMA–CPC–Nec-1 group.We have concluded that the necroptosis could be confirmed in bone tissue necrosis induced by TNF-a after bone cement injection and also could be inhibited by composite bone cement with Nec-1.
