Pyroptosis,an inflammatory caspase-dependent programmed cell death,plays a vital role in maintaining tissue homeostasis and activating inflammatory responses.Orthodontic tooth movement(OTM)is an aseptic force-induced ...Pyroptosis,an inflammatory caspase-dependent programmed cell death,plays a vital role in maintaining tissue homeostasis and activating inflammatory responses.Orthodontic tooth movement(OTM)is an aseptic force-induced inflammatory bone remodeling process mediated by the activation of periodontal ligament(PDL)progenitor cells.However,whether and how force induces PDL progenitor cell pyroptosis,thereby influencing OTM and alveolar bone remodeling remains unknown.In this study,we found that mechanical force induced the expression of pyroptosis-related markers in rat OTM and alveolar bone remodeling process.Blocking or enhancing pyroptosis level could suppress or promote OTM and alveolar bone remodeling respectively.Using Caspase-1^(−/−)mice,we further demonstrated that the functional role of the force-induced pyroptosis in PDL progenitor cells depended on Caspase-1.Moreover,mechanical force could also induce pyroptosis in human ex-vivo force-treated PDL progenitor cells and in compressive force-loaded PDL progenitor cells in vitro,which influenced osteoclastogenesis.Mechanistically,transient receptor potential subfamily V member 4 signaling was involved in force-induced Caspase-1-dependent pyroptosis in PDL progenitor cells.Overall,this study suggested a novel mechanism contributing to the modulation of osteoclastogenesis and alveolar bone remodeling under mechanical stimuli,indicating a promising approach to accelerate OTM by targeting Caspase-1.展开更多
Nano-engineering-based tissue regeneration and local therapeutic delivery strategies show significant potential to reduce the health and economic burden associated with craniofacial defects,including traumas and tumou...Nano-engineering-based tissue regeneration and local therapeutic delivery strategies show significant potential to reduce the health and economic burden associated with craniofacial defects,including traumas and tumours.Critical to the success of such nano-engineered non-resorbable craniofacial implants include load-bearing functioning and survival in complex local trauma conditions.Further,race to invade between multiple cells and pathogens is an important criterion that dictates the fate of the implant.In this pioneering review,we compare the therapeutic efficacy of nano-engineered titanium-based craniofacial implants towards maximised local therapy addressing bone formation/resorption,soft-tissue integration,bacterial infection and cancers/tumours.We present the various strategies to engineer titanium-based craniofacial implants in the macro-,micro-and nano-scales,using topographical,chemical,electrochemical,biological and therapeutic modifications.A particular focus is electrochemically anodised titanium implants with controlled nanotopographies that enable tailored and enhanced bioactivity and local therapeutic release.Next,we review the clinical translation challenges associated with such implants.This review will inform the readers of the latest developments and challenges related to therapeutic nano-engineered craniofacial implants.展开更多
Adult tendon stem/progenitor cells(TSPCs)are essential for tendon maintenance,regeneration,and repair,yet they become susceptible to senescence with age,impairing the self-healing capacity of tendons.In this study,we ...Adult tendon stem/progenitor cells(TSPCs)are essential for tendon maintenance,regeneration,and repair,yet they become susceptible to senescence with age,impairing the self-healing capacity of tendons.In this study,we employ a recently developed deep-learning-based efficacy prediction system to screen potential stemness-promoting and senescence-inhibiting drugs from natural products using the transcriptional signatures of stemness.The top-ranked candidate,prim-O-glucosylcimifugin(POG),a saposhnikovia root extract,could ameliorate TPSC senescent phenotypes caused by long-term passage and natural aging in rats and humans,as well as restore the self-renewal and proliferative capacities and tenogenic potential of aged TSPCs.In vivo,the systematic administration of POG or the local delivery of POG nanoparticles functionally rescued endogenous tendon regeneration and repair in aged rats to levels similar to those of normal animals.Mechanistically,POG protects TSPCs against functional impairment during both passage-induced and natural aging by simultaneously suppressing nuclear factor-κB and decreasing mTOR signaling with the induction of autophagy.Thus,the strategy of pharmacological intervention with the deep learning-predicted compound POG could rejuvenate aged TSPCs and improve the regenerative capacity of aged tendons.展开更多
基金supported by the National Natural Science Foundations of China No.82230030,No.81871492(Y.L.)and No.82170996(D.H.)Beijing International Science and Technology Cooperation Project No.Z221100002722003(Y.L.)+3 种基金Beijing Natural Science Foundation No.L23002,No.L234017(Y.L.)Ten-Thousand Talents Program No.QNBJ2019-2(Y.L.)Key R&D Plan of Ningxia Hui Autonomous Region No.2020BCG01001(Y.L.)Innovative Research Team of High-level Local Universities in Shanghai No.SHSMU-ZLCX20212402(Y.L.).
文摘Pyroptosis,an inflammatory caspase-dependent programmed cell death,plays a vital role in maintaining tissue homeostasis and activating inflammatory responses.Orthodontic tooth movement(OTM)is an aseptic force-induced inflammatory bone remodeling process mediated by the activation of periodontal ligament(PDL)progenitor cells.However,whether and how force induces PDL progenitor cell pyroptosis,thereby influencing OTM and alveolar bone remodeling remains unknown.In this study,we found that mechanical force induced the expression of pyroptosis-related markers in rat OTM and alveolar bone remodeling process.Blocking or enhancing pyroptosis level could suppress or promote OTM and alveolar bone remodeling respectively.Using Caspase-1^(−/−)mice,we further demonstrated that the functional role of the force-induced pyroptosis in PDL progenitor cells depended on Caspase-1.Moreover,mechanical force could also induce pyroptosis in human ex-vivo force-treated PDL progenitor cells and in compressive force-loaded PDL progenitor cells in vitro,which influenced osteoclastogenesis.Mechanistically,transient receptor potential subfamily V member 4 signaling was involved in force-induced Caspase-1-dependent pyroptosis in PDL progenitor cells.Overall,this study suggested a novel mechanism contributing to the modulation of osteoclastogenesis and alveolar bone remodeling under mechanical stimuli,indicating a promising approach to accelerate OTM by targeting Caspase-1.
基金supported by the National Natural Science Foundations of China 82230030 and 81871492(Y.L.)Beijing International Science and Technology Cooperation Project No.Z221100002722003(Y.L.)+3 种基金Ten-Thousand Talents Program QNBJ2019–2(Y.L.)Key R&D Plan of Ningxia Hui Autonomous Region 2020BCG01001(Y.L.)Innovative Research Team of High-level Local Universities in Shanghai SHSMUZLCX20212402(Y.L.)the National Health and Medical Research Council Early Career Fellowship APP1140699(K.G.)。
文摘Nano-engineering-based tissue regeneration and local therapeutic delivery strategies show significant potential to reduce the health and economic burden associated with craniofacial defects,including traumas and tumours.Critical to the success of such nano-engineered non-resorbable craniofacial implants include load-bearing functioning and survival in complex local trauma conditions.Further,race to invade between multiple cells and pathogens is an important criterion that dictates the fate of the implant.In this pioneering review,we compare the therapeutic efficacy of nano-engineered titanium-based craniofacial implants towards maximised local therapy addressing bone formation/resorption,soft-tissue integration,bacterial infection and cancers/tumours.We present the various strategies to engineer titanium-based craniofacial implants in the macro-,micro-and nano-scales,using topographical,chemical,electrochemical,biological and therapeutic modifications.A particular focus is electrochemically anodised titanium implants with controlled nanotopographies that enable tailored and enhanced bioactivity and local therapeutic release.Next,we review the clinical translation challenges associated with such implants.This review will inform the readers of the latest developments and challenges related to therapeutic nano-engineered craniofacial implants.
基金supported by the National Natural Science Foundations of China 82230030 and 81871492(Y.L.),82201020(Y.W),and 82100980(S.S.J)the Beijing Natural Science Foundation JL23002(Y.L.)and 7214305(S.S.J)+6 种基金the Beijing International Science and Technology Cooperation Project Z221100002722003(Y.L.)the Innovative Research Team of High-level Local Universities in Shanghai SHSMU-ZLCX20212402(Y.L.)Ten-Thousand Talents Program QNBJ2019-2(Y.L.)the Key R&D Plan of Ningxia Hui Autonomous Region 2020BCG01001(Y.L.)Beijing Nova Program Z211100002121043(Y.W.)China National Postdoctoral Program for Innovative Talents BX2021022(Y.W.),BX20200020(S.S.J)China Postdoctoral Science Foundation 2021M700281(Y.W.)。
文摘Adult tendon stem/progenitor cells(TSPCs)are essential for tendon maintenance,regeneration,and repair,yet they become susceptible to senescence with age,impairing the self-healing capacity of tendons.In this study,we employ a recently developed deep-learning-based efficacy prediction system to screen potential stemness-promoting and senescence-inhibiting drugs from natural products using the transcriptional signatures of stemness.The top-ranked candidate,prim-O-glucosylcimifugin(POG),a saposhnikovia root extract,could ameliorate TPSC senescent phenotypes caused by long-term passage and natural aging in rats and humans,as well as restore the self-renewal and proliferative capacities and tenogenic potential of aged TSPCs.In vivo,the systematic administration of POG or the local delivery of POG nanoparticles functionally rescued endogenous tendon regeneration and repair in aged rats to levels similar to those of normal animals.Mechanistically,POG protects TSPCs against functional impairment during both passage-induced and natural aging by simultaneously suppressing nuclear factor-κB and decreasing mTOR signaling with the induction of autophagy.Thus,the strategy of pharmacological intervention with the deep learning-predicted compound POG could rejuvenate aged TSPCs and improve the regenerative capacity of aged tendons.
