Plp1-lineage Schwann cells(SCs)of peripheral nerve play a critical role in vascular remodeling and osteogenic differentiation during the early stage of bone healing,and the abnormal plasticity of SCs would jeopardize ...Plp1-lineage Schwann cells(SCs)of peripheral nerve play a critical role in vascular remodeling and osteogenic differentiation during the early stage of bone healing,and the abnormal plasticity of SCs would jeopardize the bone regeneration.However,how Plp1-lineage cells respond to injury and initiate the vascularized osteogenesis remains incompletely understood.Here,by employing single-cell transcriptional profiling combined with lineage-specific tracing models,we uncover that Plp1-lineage cells undergoing injury-induced glia-to-MSCs transition contributed to osteogenesis and revascularization in the initial stage of bone injury.Importantly,our data demonstrated that the Sonic hedgehog(Shh)signaling was responsible for the transition process initiation,which was strongly activated by c-Jun/SIRT6/BAF170 complex-driven Shh enhancers.Collectively,these findings depict an injuryspecific niche signal-mediated Plp1-lineage cells transition towards Gli1+MSCs and may be instructive for approaches to promote bone regeneration during aging or other bone diseases.展开更多
Periodontitis imparting the increased risk of atherosclerotic cardiovascular diseases is partially due to the immune subversion of the oral pathogen,particularly the Porphyromonas gingivalis(P.gingivalis),by inducing ...Periodontitis imparting the increased risk of atherosclerotic cardiovascular diseases is partially due to the immune subversion of the oral pathogen,particularly the Porphyromonas gingivalis(P.gingivalis),by inducing apoptosis.However,it remains obscure whether accumulated apoptotic cells in P.gingivalis-accelerated plaque formation are associated with impaired macrophage clearance.展开更多
Bone defect repair remains a great challenge in the field of orthopedics.Human body essential trace element such as copper is essential for bone regeneration,but how to use it in bone defects and the underlying its me...Bone defect repair remains a great challenge in the field of orthopedics.Human body essential trace element such as copper is essential for bone regeneration,but how to use it in bone defects and the underlying its mechanisms of promoting bone formation need to be further explored.In this study,by doping copper into mesoporous bioactive glass nanoparticles(Cu-MBGNs),we unveil a previously unidentified role of copper in facilitating osteoblast mitophagy and mitochondrial dynamics,which enhance amorphous calcium phosphate(ACP)release and subsequent biomineralization,ultimately accelerating the process of bone regeneration.Specifically,by constructing conditional knockout mice lacking the autophagy gene Atg5 in osteogenic lineage cells,we first confirmed the role of Cu-MBGNs-promoted bone formation via mediating osteoblast autophagy pathway.Then,the in vitro studies revealed that Cu-MBGNs strengthened mitophagy by inducing ROS production and recruiting PINK1/Parkin,thereby facilitating the efficient release of ACP from mitochondria into matrix vesicles for bio-mineralization during bone regeneration.Moreover,we found that Cu-MBGNs promoted mitochondrion fission via activating dynamin related protein 1(Drp1)to reinforce mitophagy pathway.Together,this study highlights the potential of Cu-MBGNs-mediated mitophagy and biomineralization for augmenting bone regeneration,of-fering a promising avenue for the development of advanced bioactive materials in orthopedic applications.展开更多
基金supported by the National Natural Science Foundation of China(grants 81970910 and 82370931)Jiangsu Province Capability Improvement Project through Science,Technology and Education-Jiangsu Provincial Research Hospital Cultivation Unit(YJXYYJSDW4)Jiangsu Provincial Medical Innovation Center(CXZX202227).
文摘Plp1-lineage Schwann cells(SCs)of peripheral nerve play a critical role in vascular remodeling and osteogenic differentiation during the early stage of bone healing,and the abnormal plasticity of SCs would jeopardize the bone regeneration.However,how Plp1-lineage cells respond to injury and initiate the vascularized osteogenesis remains incompletely understood.Here,by employing single-cell transcriptional profiling combined with lineage-specific tracing models,we uncover that Plp1-lineage cells undergoing injury-induced glia-to-MSCs transition contributed to osteogenesis and revascularization in the initial stage of bone injury.Importantly,our data demonstrated that the Sonic hedgehog(Shh)signaling was responsible for the transition process initiation,which was strongly activated by c-Jun/SIRT6/BAF170 complex-driven Shh enhancers.Collectively,these findings depict an injuryspecific niche signal-mediated Plp1-lineage cells transition towards Gli1+MSCs and may be instructive for approaches to promote bone regeneration during aging or other bone diseases.
基金supported by the National Natural Science Foundation of China(grants82001012,81970910,and 81771092)the Natural Science Foundation of the Jiangsu Higher Education Institutions of China(grants 19KJA360003)China Postdoctoral Science Foundation(2021M691640)。
文摘Periodontitis imparting the increased risk of atherosclerotic cardiovascular diseases is partially due to the immune subversion of the oral pathogen,particularly the Porphyromonas gingivalis(P.gingivalis),by inducing apoptosis.However,it remains obscure whether accumulated apoptotic cells in P.gingivalis-accelerated plaque formation are associated with impaired macrophage clearance.
基金supported by the National Natural Science Foundation of China(81771092,81970910 and 82370931)Jiangsu Province Capability Improvement Project through Science,Technology and Education-Jiangsu Provincial Research Hospital Cultivation Unit(YJXYYJSDW4)Jiangsu Provincial Medical Innovation Center(CXZX202227).
文摘Bone defect repair remains a great challenge in the field of orthopedics.Human body essential trace element such as copper is essential for bone regeneration,but how to use it in bone defects and the underlying its mechanisms of promoting bone formation need to be further explored.In this study,by doping copper into mesoporous bioactive glass nanoparticles(Cu-MBGNs),we unveil a previously unidentified role of copper in facilitating osteoblast mitophagy and mitochondrial dynamics,which enhance amorphous calcium phosphate(ACP)release and subsequent biomineralization,ultimately accelerating the process of bone regeneration.Specifically,by constructing conditional knockout mice lacking the autophagy gene Atg5 in osteogenic lineage cells,we first confirmed the role of Cu-MBGNs-promoted bone formation via mediating osteoblast autophagy pathway.Then,the in vitro studies revealed that Cu-MBGNs strengthened mitophagy by inducing ROS production and recruiting PINK1/Parkin,thereby facilitating the efficient release of ACP from mitochondria into matrix vesicles for bio-mineralization during bone regeneration.Moreover,we found that Cu-MBGNs promoted mitochondrion fission via activating dynamin related protein 1(Drp1)to reinforce mitophagy pathway.Together,this study highlights the potential of Cu-MBGNs-mediated mitophagy and biomineralization for augmenting bone regeneration,of-fering a promising avenue for the development of advanced bioactive materials in orthopedic applications.
