For bone regenerative engineering,it is a promising method to form skeletal tissues differentiating from human bone morrow mesenchyme stem cells(hBMSCs).However,it is still a critical challenge to efficiently control ...For bone regenerative engineering,it is a promising method to form skeletal tissues differentiating from human bone morrow mesenchyme stem cells(hBMSCs).However,it is still a critical challenge to efficiently control ostogenesis and clearly reveal the influence factor.To this end,the fluorescent gold nanodots(Au NDs) with highly negative charges as osteogenic induction reagent are successfully synthesized,which display better than commercial osteogenic induction medium through the investigations of ALP activity(2.5 folds) and cytoskeleton staining(1.5 folds).Two kinds of oligopeptides with different bio-structures(cysteine,Cys and glutathione,GSH) are selected for providing surficial charges on Au NDs.It is revealed that Au-Cys with more negative charges(-51 mV) play better role than Au-GSH(-19 mV) in osteogenic differentiation,when both of them have same size(~2 nm),sphere shape and show similar cell uptake amount.To explore deeply,osteogenesis related signaling pathways are monitored,revealing that the enhancement of osteogenic differentiation was through autophagy signaling pathway triggered by Au-Cys.And the promotion of highly negative charges in osteogenic diffe rentiation was further proved via sliver nanodots(Ag NDs,Ag-Cys and Ag-GSH) and carbon nanodots(CDs,Cys-CDs and GSH-CDs).This work indicates part of insights during hBMSCs differentiation and provides a novel strategy in osteogenic differentiation process.展开更多
Bone marrow mesenchymal stem cells(BMSCs)are non-hematopoietic multipotent stem cells capable of differentiating into mature cells.Isoquercetin,an extract from natural sources,has shown promise as a potential treatmen...Bone marrow mesenchymal stem cells(BMSCs)are non-hematopoietic multipotent stem cells capable of differentiating into mature cells.Isoquercetin,an extract from natural sources,has shown promise as a potential treatment for osteoporosis.To investigate the therapeutic effects of isoquercetin on osteoporosis,bone marrow mesenchymal stem cells(BMSCs)were cultured in vitro,and osteogenesis or adipogenesis was induced in the presence of isoquercetin for 14 days.We evaluated cell viability,osteogenic and adipogenic differentiation,as well as mRNA expression levels of Runx2,Alpl,and OCN in osteoblasts,and mRNA expression levels of Pparγ,Fabp4,and Cebpαin adipocytes.The results showed that isoquercetin dose-dependently increased cell viability and promoted osteogenic differentiation,as evidenced by Alizarin Red and alkaline phosphatase staining and mRNA expression levels of Runx2,Alpl,and OCN in osteoblasts(P<0.05).In contrast,isoquercetin inhibited adipogenic differentiation and decreased the mRNA expres-sion levels of Pparγ,Fabp4,and Cebpαin adipocytes(P<0.05).In vivo,isoquercetin treatment increased bone quan-tity and density in an osteoporosis model mice group,as determined byμCT scanning and immunohistochemistry(P<0.05).These findings suggest that isoquercetin may have therapeutic potential for osteoporosis by promoting the proliferation and differentiation of BMSCs towards osteoblasts while inhibiting adipogenic differentiation.展开更多
The periosteum,a fibrous tissue membrane covering bone surfaces,is critical to osteogenesis and angiogenesis in bone reconstruction.Artificial periostea have been widely developed for bone defect repair,but most of th...The periosteum,a fibrous tissue membrane covering bone surfaces,is critical to osteogenesis and angiogenesis in bone reconstruction.Artificial periostea have been widely developed for bone defect repair,but most of these are lacking of periosteal bioactivity.Herein,a biomimetic periosteum(termed PEC-Apt-NP-Exo)is prepared based on an electrospun membrane combined with engineered exosomes(Exos).The electrospun membrane is fabricated using poly(ε-caprolactone)(core)-periosteal decellularized extracellular matrix(shell)fibers via coaxial elec-trospinning,to mimic the fibrous structure,mechanical property,and tissue microenvironment of natural periosteum.The engineered Exos derived from M2 macrophages are functionalized by surface modification of bone marrow mesenchymal stem cell(BMSC)-specific aptamers to further enhance cell recruitment,immuno-regulation,and angiogenesis in bone healing.The engineered Exos are covalently bonded to the electrospun membrane,to achieve rich loading and long-term effects of Exos.In vitro experiments demonstrate that the biomimetic periosteum promotes BMSC migration and osteogenic differentiation via Rap1/PI3K/AKT signaling pathway,and enhances vascular endothelial growth factor secretion from BMSCs to facilitate angiogenesis.In vivo studies reveal that the biomimetic periosteum promotes new bone formation in large bone defect repair by inducing M2 macrophage polarization,endogenous BMSC recruitment,osteogenic differentiation,and vascu-larization.This research provides valuable insights into the development of a multifunctional biomimetic peri-osteum for bone regeneration.展开更多
基金supported by the National Nature Science Foundation of China(Nos.51861145311,22005338)Science Foundation of China University of Petroleum,Beijing(No.2462017YJRC027)Open Project of State Key Laboratory of Superhard Materials(Jilin University 201802)。
文摘For bone regenerative engineering,it is a promising method to form skeletal tissues differentiating from human bone morrow mesenchyme stem cells(hBMSCs).However,it is still a critical challenge to efficiently control ostogenesis and clearly reveal the influence factor.To this end,the fluorescent gold nanodots(Au NDs) with highly negative charges as osteogenic induction reagent are successfully synthesized,which display better than commercial osteogenic induction medium through the investigations of ALP activity(2.5 folds) and cytoskeleton staining(1.5 folds).Two kinds of oligopeptides with different bio-structures(cysteine,Cys and glutathione,GSH) are selected for providing surficial charges on Au NDs.It is revealed that Au-Cys with more negative charges(-51 mV) play better role than Au-GSH(-19 mV) in osteogenic differentiation,when both of them have same size(~2 nm),sphere shape and show similar cell uptake amount.To explore deeply,osteogenesis related signaling pathways are monitored,revealing that the enhancement of osteogenic differentiation was through autophagy signaling pathway triggered by Au-Cys.And the promotion of highly negative charges in osteogenic diffe rentiation was further proved via sliver nanodots(Ag NDs,Ag-Cys and Ag-GSH) and carbon nanodots(CDs,Cys-CDs and GSH-CDs).This work indicates part of insights during hBMSCs differentiation and provides a novel strategy in osteogenic differentiation process.
基金the National Natural Science Foundation of China(Grant Nos.22276221,21675176)the Fundamental Research Funds for the Central Universities,and South-Central Minzu University(Grant No.CZP21002)for financial support.
文摘Bone marrow mesenchymal stem cells(BMSCs)are non-hematopoietic multipotent stem cells capable of differentiating into mature cells.Isoquercetin,an extract from natural sources,has shown promise as a potential treatment for osteoporosis.To investigate the therapeutic effects of isoquercetin on osteoporosis,bone marrow mesenchymal stem cells(BMSCs)were cultured in vitro,and osteogenesis or adipogenesis was induced in the presence of isoquercetin for 14 days.We evaluated cell viability,osteogenic and adipogenic differentiation,as well as mRNA expression levels of Runx2,Alpl,and OCN in osteoblasts,and mRNA expression levels of Pparγ,Fabp4,and Cebpαin adipocytes.The results showed that isoquercetin dose-dependently increased cell viability and promoted osteogenic differentiation,as evidenced by Alizarin Red and alkaline phosphatase staining and mRNA expression levels of Runx2,Alpl,and OCN in osteoblasts(P<0.05).In contrast,isoquercetin inhibited adipogenic differentiation and decreased the mRNA expres-sion levels of Pparγ,Fabp4,and Cebpαin adipocytes(P<0.05).In vivo,isoquercetin treatment increased bone quan-tity and density in an osteoporosis model mice group,as determined byμCT scanning and immunohistochemistry(P<0.05).These findings suggest that isoquercetin may have therapeutic potential for osteoporosis by promoting the proliferation and differentiation of BMSCs towards osteoblasts while inhibiting adipogenic differentiation.
基金the National Natural Science Foundation of China(Grant No.82301025)the Talents Introduction of Guangdong Provincial People’s Hospital(Grant Nos.KY0120220255,3227100558,8237030185)+4 种基金Guangzhou Municipal Science and Technology Bureau(Grant No.2024A04J4888)the National Key Research and Development Program of China(Grant No.2023YFC2413600)the Natural Science Foundation of Guangdong Province(Grant No.2022A1515110916)the GJYC pro-gram of Guangzhou(Grant No.2024D03J0004)the National Nat-ural Science Foundation of China(Grant No.52433010).
文摘The periosteum,a fibrous tissue membrane covering bone surfaces,is critical to osteogenesis and angiogenesis in bone reconstruction.Artificial periostea have been widely developed for bone defect repair,but most of these are lacking of periosteal bioactivity.Herein,a biomimetic periosteum(termed PEC-Apt-NP-Exo)is prepared based on an electrospun membrane combined with engineered exosomes(Exos).The electrospun membrane is fabricated using poly(ε-caprolactone)(core)-periosteal decellularized extracellular matrix(shell)fibers via coaxial elec-trospinning,to mimic the fibrous structure,mechanical property,and tissue microenvironment of natural periosteum.The engineered Exos derived from M2 macrophages are functionalized by surface modification of bone marrow mesenchymal stem cell(BMSC)-specific aptamers to further enhance cell recruitment,immuno-regulation,and angiogenesis in bone healing.The engineered Exos are covalently bonded to the electrospun membrane,to achieve rich loading and long-term effects of Exos.In vitro experiments demonstrate that the biomimetic periosteum promotes BMSC migration and osteogenic differentiation via Rap1/PI3K/AKT signaling pathway,and enhances vascular endothelial growth factor secretion from BMSCs to facilitate angiogenesis.In vivo studies reveal that the biomimetic periosteum promotes new bone formation in large bone defect repair by inducing M2 macrophage polarization,endogenous BMSC recruitment,osteogenic differentiation,and vascu-larization.This research provides valuable insights into the development of a multifunctional biomimetic peri-osteum for bone regeneration.
