After injury,bone tissue initiates a reparative response to restore its structure and function.The failure to initiate or delay this response could result in fracture nonunion.The molecular mechanisms underlying the o...After injury,bone tissue initiates a reparative response to restore its structure and function.The failure to initiate or delay this response could result in fracture nonunion.The molecular mechanisms underlying the occurrence of fracture nonunion are not yet established.We propose that hypoxia-triggered signaling pathways,mediated by reactive oxygen species(ROS)homeostasis,control Bmp2 expression and fracture healing initiation.The excessive ROS leads to oxidative stress and,ultimately,fracture nonunion.In this study,we silenced Apex1,the final ROS signaling transducer that mediates the activation of key transcription factors by their cysteines oxidoreduction,evaluating its role during endochondral ossification and fracture repair.Silencing Apex1 in limb bud mesenchyme results in transient metaphyseal dysplasia derived from impaired chondrocyte differentiation.During bone regeneration,Apex1 silencing induces a fracture nonunion phenotype,characterized by delayed fracture repair initiation,impaired periosteal response,and reduced chondrocyte and osteoblast differentiation.This compromised chondrocyte differentiation hampers callus vascularization and healing progression.Our findings highlight a critical mechanism where hypoxia-driven ROS signaling in mesenchymal progenitors through APEX1 is essential for fracture healing initiation.展开更多
The success rate of apexification is primarily determined by multiple factors,including the material used,the size of the open apex compared to the length of the root,and the technique used in each case.The main objec...The success rate of apexification is primarily determined by multiple factors,including the material used,the size of the open apex compared to the length of the root,and the technique used in each case.The main objective of this review was to provide an update on the present management of open apex to identify factors and circumstances that may influence the success of apexification using different materials and techniques.Future research on apexification should focus on how to treat open apices with wide periapical lesions without surgery.Previously,the predictability of these parameters with non-surgical procedures was uncertain,but now,with the use of a dental operating microscope,it has become more predictable.Another reason could be that extra visits are no longer required due to major advances in the armamentarium and materials used for apexification.展开更多
基金supported by funds of the Ministerio de Ciencia, Innovación y Universidadesco-financed by European Regional Development Fund-FEDER “A way to make Europe” (Project Ref:PID2023-153309OB-I00) supported by MCIN/AEl/ 10.13039/501100011033/ FEDER, UE+10 种基金Ministerio de Ciencia, Innovación y Universidades through Instituto de Salud Carlos Ⅲ and European Regional Development Funds “A way to make Europe” (PI17/00136, PI20/00076)European Union Horizon 2020 program (grant agreement #874889, HEALIKICK) to F. Granero-MoltóNext Generation EU, Plan de Recuperación, Transformación y Resiliencia RICORS TERAV ISCIII (RD21/0017/0009)H2020-MSCA-RISE-2019 (grant agreement #872648, MEPHOS) to F. Próspersupported by a fellowship from “Asociación de Amigos de la Universidad de Navarra”supported by a fellowship CIMA AC from “Fundación para la Investigación Médica Aplicada”funded by grants PID2022-104776RB-100 and CB16/11/00399 (CIBER CV) from MCIN/AEI/10.13039/501100011033La Caixa Research Health Foundation (Ref. HR23-00084)supported by a fellowship of “Asociación de Amigos de la Universidad de Navarra” and “Obra Social La Caixa”the research leading to these results has received funding from “la Caixa” Banking Foundationsupported by a Sara Borrell grant (CD22/00027) from the Instituto Carlos Ⅲ and Next Generation EU。
文摘After injury,bone tissue initiates a reparative response to restore its structure and function.The failure to initiate or delay this response could result in fracture nonunion.The molecular mechanisms underlying the occurrence of fracture nonunion are not yet established.We propose that hypoxia-triggered signaling pathways,mediated by reactive oxygen species(ROS)homeostasis,control Bmp2 expression and fracture healing initiation.The excessive ROS leads to oxidative stress and,ultimately,fracture nonunion.In this study,we silenced Apex1,the final ROS signaling transducer that mediates the activation of key transcription factors by their cysteines oxidoreduction,evaluating its role during endochondral ossification and fracture repair.Silencing Apex1 in limb bud mesenchyme results in transient metaphyseal dysplasia derived from impaired chondrocyte differentiation.During bone regeneration,Apex1 silencing induces a fracture nonunion phenotype,characterized by delayed fracture repair initiation,impaired periosteal response,and reduced chondrocyte and osteoblast differentiation.This compromised chondrocyte differentiation hampers callus vascularization and healing progression.Our findings highlight a critical mechanism where hypoxia-driven ROS signaling in mesenchymal progenitors through APEX1 is essential for fracture healing initiation.
文摘The success rate of apexification is primarily determined by multiple factors,including the material used,the size of the open apex compared to the length of the root,and the technique used in each case.The main objective of this review was to provide an update on the present management of open apex to identify factors and circumstances that may influence the success of apexification using different materials and techniques.Future research on apexification should focus on how to treat open apices with wide periapical lesions without surgery.Previously,the predictability of these parameters with non-surgical procedures was uncertain,but now,with the use of a dental operating microscope,it has become more predictable.Another reason could be that extra visits are no longer required due to major advances in the armamentarium and materials used for apexification.
