Given afferent functions,sensory nerves have recently been found to exert efferent effects and directly alter organ physiology.Additionally,several studies have highlighted the indirect but crucial role of sensory ner...Given afferent functions,sensory nerves have recently been found to exert efferent effects and directly alter organ physiology.Additionally,several studies have highlighted the indirect but crucial role of sensory nerves in the regulation of the physiological function of osteoclasts.Nonetheless,evidence regarding the direct sensory nerve efferent influence on osteoclasts is lacking.In the current study,we found that high levels of efferent signals were transported directly from the sensory nerves into osteoclasts.Furthermore,sensory hypersensitivity significantly increased osteoclastic bone resorption,and sensory neurons(SNs)directly promoted osteoclastogenesis in an in vitro coculture system.Moreover,we screened a novel neuropeptide,Cyp40,using an isobaric tag for relative and absolute quantitation(iTRAQ).We observed that Cyp40 is the efferent signal from sensory nerves,and it plays a critical role in osteoclastogenesis via the aryl hydrocarbon receptor(AhR)-Ras/Raf-p-Erk-NFATc1 pathway.These findings revealed a novel mechanism regarding the influence of sensory nerves on bone regulation,i.e.,a direct promoting effect on osteoclastogenesis by the secretion of Cyp40.Therefore,inhibiting Cyp40 could serve as a strategy to improve bone quality in osteoporosis and promote bone repair after bone injury.展开更多
The authors regret a mistake of funding numbers in the Acknowledgment Section failed to be corrected during proofreading.Below is the corrected funding statement in ACKNOWLEDGMENT SECTION:This work was supported by th...The authors regret a mistake of funding numbers in the Acknowledgment Section failed to be corrected during proofreading.Below is the corrected funding statement in ACKNOWLEDGMENT SECTION:This work was supported by the National Natural Science Foundation of China(NSFC)(Nos.82072415,81772354,81902189),Clinical Innovation Research Program of Guangzhou Regenerative Medicine and Health Guangdong Laboratory(2018GZR0201002),Science Technology Project of Guangzhou City(2019ZD15).展开更多
The potential translation of bio-inert polymer scaffolds as bone substitutes is limited by the lack of neovascularization upon implantation and subsequently diminished ingrowth of host bone,most likely resulted from t...The potential translation of bio-inert polymer scaffolds as bone substitutes is limited by the lack of neovascularization upon implantation and subsequently diminished ingrowth of host bone,most likely resulted from the inability to replicate appropriate endogenous crosstalk between cells.Human umbilical vein endothelial cell-derived decellularized extracellular matrix(HdECM),which contains a collection of angiocrine biomolecules,has recently been demonstrated to mediate endothelial cells(ECs)-osteoprogenitors(OPs)crosstalk.We employed the HdECM to create a PCL(polycaprolactone)/fibrin/HdECM(PFE)hybrid scaffold.We hypothesized PFE scaffold could reconstitute a bio-instructive microenvironment that reintroduces the crosstalk,resulting in vascularized bone regeneration.Following implantation in a rat femoral bone defect,the PFE scaffold demonstrated early vascular infiltration and enhanced bone regeneration by microangiography(μ-AG)and micro-computational tomography(μ-CT).Based on the immunofluorescence studies,PFE mediated the endogenous angiogenesis and osteogenesis with a substantial number of type H vessels and osteoprogenitors.In addition,superior osseointegration was observed by a direct host bone-PCL interface,which was likely attributed to the formation of type H vessels.The bio-instructive microenvironment created by our innovative PFE scaffold made possible superior osseointegration and type H vessel-related bone regeneration.It could become an alternative solution of improving the osseointegration of bone substitutes with the help of induced type H vessels,which could compensate for the inherent biological inertness of synthetic polymers.展开更多
The technique bottleneck of repairing large bone defects with tissue engineered bone is the vascularization of tissue engineered grafts.Although some studies have shown that extracellular vesicles(EVs)derived from bon...The technique bottleneck of repairing large bone defects with tissue engineered bone is the vascularization of tissue engineered grafts.Although some studies have shown that extracellular vesicles(EVs)derived from bone marrow mesenchymal stem cells(BMSCs)promote bone healing and repair by accelerating angiogenesis,the effector molecules and the mechanism remain unclear,which fail to provide ideas for the future research and development of cell-free interventions.Here,we found that Nidogen1-enriched EV(EV-NID1)derived from BMSCs interferes with the formation and assembly of focal adhesions(FAs)by targeting myosin-10,thereby reducing the adhesion strength of rat arterial endothelial cells(RAECs)to the extracellular matrix(ECM),and enhancing the migration and angiogenesis potential of RAECs.Moreover,by delivery with composite hydrogel,EV-NID1 is demonstrated to promote angiogenesis and bone regeneration in rat femoral defects.This study identifies the intracellular binding target of EV-NID1 and further elucidates a novel approach and mechanism,thereby providing a cell-free construction strategy with precise targets for the development of vascularized tissue engineering products.展开更多
Developments of digital technology and three-dimensional(3D)reconstruction allowed a precise description of anatomic structures.With the introduction of Visible Human Project and Virtual Chinese Human(VCH)techniques,m...Developments of digital technology and three-dimensional(3D)reconstruction allowed a precise description of anatomic structures.With the introduction of Visible Human Project and Virtual Chinese Human(VCH)techniques,more detailed anatomic images could be obtained.Digitized visible models of these structures can be applied as a useful tool in clinical training.The aim of this study was to reconstruct the normal structures of thoracodorsal artery in 3D images and to establish the digitized visible models of latissimus dorsi myocutaneous(LDM)flap.The cross-sectional images from the four VCH datasets were reviewed to study LDM and thoraco-dorsal artery structures on a section-by-section basis.Next,two adult fresh cadaver specimens were perfused with lead oxide-gelatine mixture and subject to radio-graphic CT scanning on their torsos.The cross-sectional images from the CT images were reviewed to study thor-acodorsal artery structures.Three-dimensional computer-ized reconstructions of LDM flap structures were conducted from these datasets by using Amira 3.1(TGS)software respectively.The 3D reconstructed visible models established from these datasets perfectly displayed the anatomic characteristics of LDM flap.展开更多
基金the NSFC Key Program of the National Natural Science Foundation of China(Grant No.81430049)the NSFC General Program of the National Natural Science Foundation of China(Grant Nos.81772377 and 81972045)+1 种基金the NSFC Youth Program of the National Natural Science Foundation of China(Grant No.81902202)supported by Shenzhen Science and Technology Program(CN)(No.SGDX20211123114204007)。
文摘Given afferent functions,sensory nerves have recently been found to exert efferent effects and directly alter organ physiology.Additionally,several studies have highlighted the indirect but crucial role of sensory nerves in the regulation of the physiological function of osteoclasts.Nonetheless,evidence regarding the direct sensory nerve efferent influence on osteoclasts is lacking.In the current study,we found that high levels of efferent signals were transported directly from the sensory nerves into osteoclasts.Furthermore,sensory hypersensitivity significantly increased osteoclastic bone resorption,and sensory neurons(SNs)directly promoted osteoclastogenesis in an in vitro coculture system.Moreover,we screened a novel neuropeptide,Cyp40,using an isobaric tag for relative and absolute quantitation(iTRAQ).We observed that Cyp40 is the efferent signal from sensory nerves,and it plays a critical role in osteoclastogenesis via the aryl hydrocarbon receptor(AhR)-Ras/Raf-p-Erk-NFATc1 pathway.These findings revealed a novel mechanism regarding the influence of sensory nerves on bone regulation,i.e.,a direct promoting effect on osteoclastogenesis by the secretion of Cyp40.Therefore,inhibiting Cyp40 could serve as a strategy to improve bone quality in osteoporosis and promote bone repair after bone injury.
文摘The authors regret a mistake of funding numbers in the Acknowledgment Section failed to be corrected during proofreading.Below is the corrected funding statement in ACKNOWLEDGMENT SECTION:This work was supported by the National Natural Science Foundation of China(NSFC)(Nos.82072415,81772354,81902189),Clinical Innovation Research Program of Guangzhou Regenerative Medicine and Health Guangdong Laboratory(2018GZR0201002),Science Technology Project of Guangzhou City(2019ZD15).
基金This work was supported by the National Natural Science Foundation of China(NSFC)(Nos.82072415,81772354,81902189)Clinical Innovation Research Program of Guangzhou Regenerative Medicine and Health Guangdong Laboratory(2018GZR0201001)+3 种基金Science Technology Project of Guangzhou City(2019ZD15)Collegiate Innovation and Entrepreneurship Education Project of Guangzhou City(2019PT104)Science and Technology Innovation Project of Foshan City(1920001000025)and National Young Thousand-Talent Scheme to Zhang Zhi-Yong.
文摘The potential translation of bio-inert polymer scaffolds as bone substitutes is limited by the lack of neovascularization upon implantation and subsequently diminished ingrowth of host bone,most likely resulted from the inability to replicate appropriate endogenous crosstalk between cells.Human umbilical vein endothelial cell-derived decellularized extracellular matrix(HdECM),which contains a collection of angiocrine biomolecules,has recently been demonstrated to mediate endothelial cells(ECs)-osteoprogenitors(OPs)crosstalk.We employed the HdECM to create a PCL(polycaprolactone)/fibrin/HdECM(PFE)hybrid scaffold.We hypothesized PFE scaffold could reconstitute a bio-instructive microenvironment that reintroduces the crosstalk,resulting in vascularized bone regeneration.Following implantation in a rat femoral bone defect,the PFE scaffold demonstrated early vascular infiltration and enhanced bone regeneration by microangiography(μ-AG)and micro-computational tomography(μ-CT).Based on the immunofluorescence studies,PFE mediated the endogenous angiogenesis and osteogenesis with a substantial number of type H vessels and osteoprogenitors.In addition,superior osseointegration was observed by a direct host bone-PCL interface,which was likely attributed to the formation of type H vessels.The bio-instructive microenvironment created by our innovative PFE scaffold made possible superior osseointegration and type H vessel-related bone regeneration.It could become an alternative solution of improving the osseointegration of bone substitutes with the help of induced type H vessels,which could compensate for the inherent biological inertness of synthetic polymers.
基金supported by the National Natural Science Foundation of China(Project no.81902202,81772377,81430049 and 81902263).
文摘The technique bottleneck of repairing large bone defects with tissue engineered bone is the vascularization of tissue engineered grafts.Although some studies have shown that extracellular vesicles(EVs)derived from bone marrow mesenchymal stem cells(BMSCs)promote bone healing and repair by accelerating angiogenesis,the effector molecules and the mechanism remain unclear,which fail to provide ideas for the future research and development of cell-free interventions.Here,we found that Nidogen1-enriched EV(EV-NID1)derived from BMSCs interferes with the formation and assembly of focal adhesions(FAs)by targeting myosin-10,thereby reducing the adhesion strength of rat arterial endothelial cells(RAECs)to the extracellular matrix(ECM),and enhancing the migration and angiogenesis potential of RAECs.Moreover,by delivery with composite hydrogel,EV-NID1 is demonstrated to promote angiogenesis and bone regeneration in rat femoral defects.This study identifies the intracellular binding target of EV-NID1 and further elucidates a novel approach and mechanism,thereby providing a cell-free construction strategy with precise targets for the development of vascularized tissue engineering products.
文摘Developments of digital technology and three-dimensional(3D)reconstruction allowed a precise description of anatomic structures.With the introduction of Visible Human Project and Virtual Chinese Human(VCH)techniques,more detailed anatomic images could be obtained.Digitized visible models of these structures can be applied as a useful tool in clinical training.The aim of this study was to reconstruct the normal structures of thoracodorsal artery in 3D images and to establish the digitized visible models of latissimus dorsi myocutaneous(LDM)flap.The cross-sectional images from the four VCH datasets were reviewed to study LDM and thoraco-dorsal artery structures on a section-by-section basis.Next,two adult fresh cadaver specimens were perfused with lead oxide-gelatine mixture and subject to radio-graphic CT scanning on their torsos.The cross-sectional images from the CT images were reviewed to study thor-acodorsal artery structures.Three-dimensional computer-ized reconstructions of LDM flap structures were conducted from these datasets by using Amira 3.1(TGS)software respectively.The 3D reconstructed visible models established from these datasets perfectly displayed the anatomic characteristics of LDM flap.
