BACKGROUND Icariin(ICA),a natural flavonoid compound monomer,has multiple pharmacological activities.However,its effect on bone defect in the context of type 1 diabetes mellitus(T1DM)has not yet been examined.AIM To e...BACKGROUND Icariin(ICA),a natural flavonoid compound monomer,has multiple pharmacological activities.However,its effect on bone defect in the context of type 1 diabetes mellitus(T1DM)has not yet been examined.AIM To explore the role and potential mechanism of ICA on bone defect in the context of T1DM.METHODS The effects of ICA on osteogenesis and angiogenesis were evaluated by alkaline phosphatase staining,alizarin red S staining,quantitative real-time polymerase chain reaction,Western blot,and immunofluorescence.Angiogenesis-related assays were conducted to investigate the relationship between osteogenesis and angiogenesis.A bone defect model was established in T1DM rats.The model rats were then treated with ICA or placebo and micron-scale computed tomography,histomorphometry,histology,and sequential fluorescent labeling were used to evaluate the effect of ICA on bone formation in the defect area.RESULTS ICA promoted bone marrow mesenchymal stem cell(BMSC)proliferation and osteogenic differentiation.The ICA treated-BMSCs showed higher expression levels of osteogenesis-related markers(alkaline phosphatase and osteocalcin)and angiogenesis-related markers(vascular endothelial growth factor A and platelet endothelial cell adhesion molecule 1)compared to the untreated group.ICA was also found to induce osteogenesis-angiogenesis coupling of BMSCs.In the bone defect model T1DM rats,ICA facilitated bone formation and CD31hiEMCNhi type H-positive capillary formation.Lastly,ICA effectively accelerated the rate of bone formation in the defect area.CONCLUSION ICA was able to accelerate bone regeneration in a T1DM rat model by inducing osteogenesis-angiogenesis coupling of BMSCs.展开更多
Metallic bone screws are clinically used to fix the fractured bone fragments in bone defect treatment;yet they present compromised therapeutic efficacy due to poor osseointegration and tissue support.Here,we develop a...Metallic bone screws are clinically used to fix the fractured bone fragments in bone defect treatment;yet they present compromised therapeutic efficacy due to poor osseointegration and tissue support.Here,we develop a novel thermoresponsive shape memory(SMP)bone screw with osteogenesis-angiogenesis coupling for enhanced bone regeneration.The SMP bone screws are prepared by die casting of shape memory polyurethane/hydroxyapatite(PU/HA)composite,coated with L-arginine(Arg)and calcium ions(Ca^(2+)).The SMP bone screw could shrink and be easily reshaped at room temperature(25◦C)and then rapidly recover to its original state(37℃),granting it robust internal fixation capacity(2-fold increase in pull-out force)and beneficial compressive force to nearby tissues.Additionally,the long-term release of L-arginine and calcium ions synergistically activate the nitric oxide-cyclic guanosine monophosphate(NO-cGMP)signaling pathway of native cells.Synergized with its shape memory function,the SMP bone screw activated calcium signaling pathway under the stimulation of mechanical stress,promote the activation of various osteogenic pathways(e.g.PI3K-Akt signaling pathway),and upregulate the NO-cGMP pathway by regulating the influx of calcium ions and arginine to synchronously coordinate osteogenesis and angiogenesis to accelerate bone repair.We envision that our slot-in,snap-back and homeothermal shape memory bone screw,with its easily reshaped and fast stress release properties and osteogenesis-angiogenesis coupling efficacy,can shed new light on the development of clinical bone screws.展开更多
The coupled process of osteogenesis-angiogenesis plays a crucial role in periodontal tissue regeneration.Although various cytokines or chemokines have been widely applied in periodontal in situ tissue engineering,most...The coupled process of osteogenesis-angiogenesis plays a crucial role in periodontal tissue regeneration.Although various cytokines or chemokines have been widely applied in periodontal in situ tissue engineering,most of them are macromolecular proteins with the drawbacks of short effective half-life,poor stability and high cost,which constrain their clinical translation.Our study aimed to develop a difunctional structure for periodontal tissue regeneration by incorporating an angiogenic small molecule,dimethyloxalylglycine(DMOG),and an osteoinductive inorganic nanomaterial,nanosilicate(nSi)into poly(lactic-co-glycolic acid)(PLGA)fibers by electrospinning.The physiochemical properties of DMOG/nSi-PLGA fibrous membranes were characterized.Thereafter,the effect of DMOG/nSi-PLGA membranes on periodontal tissue regeneration was evaluated by detecting osteogenic and angiogenic differentiation potential of periodontal ligament stem cells(PDLSCs)in vitro.Additionally,the fibrous membranes were transplanted into rat periodontal defects,and tissue regeneration was assessed with histological evaluation,micro-computed tomography(micro-CT),and immunohistochemical analysis.DMOG/nSi-PLGA membranes possessed preferable mechanical property and biocompatibility.PDLSCs seeded on the DMOG/nSi-PLGA membranes showed up-regulated expression of osteogenic and angiogenic markers,higher alkaline phosphatase(ALP)activity,and more tube formation in comparison with single application.Further,in vivo study showed that the DMOG/nSi-PLGA membranes promoted recruitment of CD90+/CD34stromal cells,induced angiogenesis and osteogenesis,and regenerated cementum-ligament-bone complex in periodontal defects.Consequently,the combination of DMOG and nSi exerted admirable effects on periodontal tissue regeneration.DMOG/nSi-PLGA fibrous membranes could enhance and orchestrate osteogenesis-angiogenesis,and may have the potential to be translated as an effective scaffold in periodontal tissue engineering.展开更多
基金Supported by the Postdoctoral Fellowship Program of China Postdoctoral Science Foundation,No.GZC20231088President Foundation of The Third Affiliated Hospital of Southern Medical University,China,No.YP202210.
文摘BACKGROUND Icariin(ICA),a natural flavonoid compound monomer,has multiple pharmacological activities.However,its effect on bone defect in the context of type 1 diabetes mellitus(T1DM)has not yet been examined.AIM To explore the role and potential mechanism of ICA on bone defect in the context of T1DM.METHODS The effects of ICA on osteogenesis and angiogenesis were evaluated by alkaline phosphatase staining,alizarin red S staining,quantitative real-time polymerase chain reaction,Western blot,and immunofluorescence.Angiogenesis-related assays were conducted to investigate the relationship between osteogenesis and angiogenesis.A bone defect model was established in T1DM rats.The model rats were then treated with ICA or placebo and micron-scale computed tomography,histomorphometry,histology,and sequential fluorescent labeling were used to evaluate the effect of ICA on bone formation in the defect area.RESULTS ICA promoted bone marrow mesenchymal stem cell(BMSC)proliferation and osteogenic differentiation.The ICA treated-BMSCs showed higher expression levels of osteogenesis-related markers(alkaline phosphatase and osteocalcin)and angiogenesis-related markers(vascular endothelial growth factor A and platelet endothelial cell adhesion molecule 1)compared to the untreated group.ICA was also found to induce osteogenesis-angiogenesis coupling of BMSCs.In the bone defect model T1DM rats,ICA facilitated bone formation and CD31hiEMCNhi type H-positive capillary formation.Lastly,ICA effectively accelerated the rate of bone formation in the defect area.CONCLUSION ICA was able to accelerate bone regeneration in a T1DM rat model by inducing osteogenesis-angiogenesis coupling of BMSCs.
基金supported by the Guangdong-Foshan Joint Fund from Guangdong Basic and Applied Basic Research Foundation(2020B15153000)the Excellent Young Scholars Projects from the National Natural Science Foundation of China(NSFC,82122002)+4 种基金General Program of NSFC(52335004,52275199)the Collaborative Research Fund(C5044-21G)NSFC/RGC Joint Research Scheme(N_PolyU526/22)from the Research Grants Council of Hong Kong,the Innovation and Technology Fund from the Innovation and Technology Commission(ITS/085/21)Beijing Natural Science Foundation(J230001,L248029)Young Scholars Program of Shandong University.
文摘Metallic bone screws are clinically used to fix the fractured bone fragments in bone defect treatment;yet they present compromised therapeutic efficacy due to poor osseointegration and tissue support.Here,we develop a novel thermoresponsive shape memory(SMP)bone screw with osteogenesis-angiogenesis coupling for enhanced bone regeneration.The SMP bone screws are prepared by die casting of shape memory polyurethane/hydroxyapatite(PU/HA)composite,coated with L-arginine(Arg)and calcium ions(Ca^(2+)).The SMP bone screw could shrink and be easily reshaped at room temperature(25◦C)and then rapidly recover to its original state(37℃),granting it robust internal fixation capacity(2-fold increase in pull-out force)and beneficial compressive force to nearby tissues.Additionally,the long-term release of L-arginine and calcium ions synergistically activate the nitric oxide-cyclic guanosine monophosphate(NO-cGMP)signaling pathway of native cells.Synergized with its shape memory function,the SMP bone screw activated calcium signaling pathway under the stimulation of mechanical stress,promote the activation of various osteogenic pathways(e.g.PI3K-Akt signaling pathway),and upregulate the NO-cGMP pathway by regulating the influx of calcium ions and arginine to synchronously coordinate osteogenesis and angiogenesis to accelerate bone repair.We envision that our slot-in,snap-back and homeothermal shape memory bone screw,with its easily reshaped and fast stress release properties and osteogenesis-angiogenesis coupling efficacy,can shed new light on the development of clinical bone screws.
基金the National Natural Science Foundation of China(No.81670993,81873716,and 81901009)The Construction Engineering Special Fund of“Taishan Scholars”of Shandong Province(No.ts20190975 and tsqn201909180)+1 种基金National Key R&D Program of China(No.2017YFB0405400)Collaborative Innovation Center of Technology and Equipment for Biological Diagnosis and Therapy in Universities of Shandong,The National Key Research and Development Program of China(No.2017YFA0104604),Open Foundation of Shandong Provincial Key Laboratory of Oral Tissue Regeneration(No.SDKQ201901,SDKQ201904).The funders had no role in study design,data collection and analysis,decision to publish or preparation of the manuscript.The authors also thank Prof.Hongyu Zhang and Dr.Yi Wang from Tsinghua University for technical guidance.The authors declare that no financial or other potential competing interests exist with regard to this study.
文摘The coupled process of osteogenesis-angiogenesis plays a crucial role in periodontal tissue regeneration.Although various cytokines or chemokines have been widely applied in periodontal in situ tissue engineering,most of them are macromolecular proteins with the drawbacks of short effective half-life,poor stability and high cost,which constrain their clinical translation.Our study aimed to develop a difunctional structure for periodontal tissue regeneration by incorporating an angiogenic small molecule,dimethyloxalylglycine(DMOG),and an osteoinductive inorganic nanomaterial,nanosilicate(nSi)into poly(lactic-co-glycolic acid)(PLGA)fibers by electrospinning.The physiochemical properties of DMOG/nSi-PLGA fibrous membranes were characterized.Thereafter,the effect of DMOG/nSi-PLGA membranes on periodontal tissue regeneration was evaluated by detecting osteogenic and angiogenic differentiation potential of periodontal ligament stem cells(PDLSCs)in vitro.Additionally,the fibrous membranes were transplanted into rat periodontal defects,and tissue regeneration was assessed with histological evaluation,micro-computed tomography(micro-CT),and immunohistochemical analysis.DMOG/nSi-PLGA membranes possessed preferable mechanical property and biocompatibility.PDLSCs seeded on the DMOG/nSi-PLGA membranes showed up-regulated expression of osteogenic and angiogenic markers,higher alkaline phosphatase(ALP)activity,and more tube formation in comparison with single application.Further,in vivo study showed that the DMOG/nSi-PLGA membranes promoted recruitment of CD90+/CD34stromal cells,induced angiogenesis and osteogenesis,and regenerated cementum-ligament-bone complex in periodontal defects.Consequently,the combination of DMOG and nSi exerted admirable effects on periodontal tissue regeneration.DMOG/nSi-PLGA fibrous membranes could enhance and orchestrate osteogenesis-angiogenesis,and may have the potential to be translated as an effective scaffold in periodontal tissue engineering.
