Objective This study aimed to explore the association of single nucleotide polymorphisms(SNP)in the matrix metalloproteinase 2(MMP-2)signaling pathway and the risk of vascular senescence(VS).Methods In this cross-sect...Objective This study aimed to explore the association of single nucleotide polymorphisms(SNP)in the matrix metalloproteinase 2(MMP-2)signaling pathway and the risk of vascular senescence(VS).Methods In this cross-sectional study,between May and November 2022,peripheral venous blood of151 VS patients(case group)and 233 volunteers(control group)were collected.Fourteen SNPs were identified in five genes encoding the components of the MMP-2 signaling pathway,assessed through carotid-femoral pulse wave velocity(cf PWV),and analyzed using multivariate logistic regression.The multigene influence on the risk of VS was assessed using multifactor dimensionality reduction(MDR)and generalized multifactor dimensionality regression(GMDR)modeling.Results Within the multivariate logistic regression models,four SNPs were screened to have significant associations with VS:chemokine(C-C motif)ligand 2(CCL2)rs4586,MMP2 rs14070,MMP2rs7201,and MMP2 rs1053605.Carriers of the T/C genotype of MMP2 rs14070 had a 2.17-fold increased risk of developing VS compared with those of the C/C genotype,and those of the T/T genotype had a19.375-fold increased risk.CCL2 rs4586 and MMP-2 rs14070 exhibited the most significant interactions.Conclusion CCL2 rs4586,MMP-2 rs14070,MMP-2 rs7201,and MMP-2 rs1053605 polymorphisms were significantly associated with the risk of VS.展开更多
The effects of various cartilage extracellular matrix on the construction of rabbit growth plate cartilage tissue in vitro were studied. The results show that collagen, proteoglycan and hyaluronic acid can promote the...The effects of various cartilage extracellular matrix on the construction of rabbit growth plate cartilage tissue in vitro were studied. The results show that collagen, proteoglycan and hyaluronic acid can promote the growth of cultured chondrocytes but the effects of various cartilage extracellular matrix(ECM)on chondrocyte differentiation are different. Collagen can promote the hypertrophy of chondrocytes while proteoglycan and hyaluronic acid inhibit the transition of mature chondrocytes into hypertrophied chondrocytes.展开更多
Extracellular matrix( ECM) plays a prominent role in establishing and maintaining an appropriate microenvironment for tissue regeneration. The aims of this study were to construct a tissue engineered scaffold by recon...Extracellular matrix( ECM) plays a prominent role in establishing and maintaining an appropriate microenvironment for tissue regeneration. The aims of this study were to construct a tissue engineered scaffold by reconstituting osteoblast cell-derived ECM( O-ECM) on the electrospun nanofibrous scaffold,and further to evaluate its subsequent application for promoting the proliferation of bone marrow mesenchymal stem cells( BMSCs). To engineer a biomimetic scaffold, calvarial osteoblasts and electrospun poly-llactic acid( PLLA) nanofibers were prepared and subjected to decellularize for O-ECM deposition. To evaluate and characterize the O-ECM/PLLA scaffold, the morphology was examined and several specific mark proteins of osteoblasts matrix were evaluated.Furthermore,the cell counting kit-8( CCK-8) assay was used to detect the proliferation of the BMSCs cultivated on the O-ECM/PLLA scaffold. The results indicated O-ECM/PLLA scaffold was loaded with Collagen I, Fibronectin, and Laminin, as the composition of the marrow ECM. After decellularization,O-ECM deposition was observed in O-ECM/PLLA scaffold. Moreover,the O-ECM/PLLA scaffold could significantly enhance the proliferation of BMSCs,suggesting better cytocompatibility compared to the other groups tested. Taken together,a biomimetic scaffold based on the joint use of O-ECM and PLLA biomaterials,which represents a promising approach to bone tissue engineering, facilitates the expansion of BMSCs in vitro.展开更多
Functional repair of injured tissue in the adult central nervous system （CNS） still remains a big challenge for current biomed- ical research and its upcoming clinical translation. The axonal regeneration of the adu...Functional repair of injured tissue in the adult central nervous system （CNS） still remains a big challenge for current biomed- ical research and its upcoming clinical translation. The axonal regeneration of the adult CNS is generally low, and it is addi- tionally restricted after injury by the presence of inhibitory mol- ecules, generated by the glial scar.展开更多
Matrix within cells,the cytoskeleton,and that which surrounds cells,the extracellular matrix（ECM）,are connected to one another through a number of receptors including those in primary cilia,serving as an important c...Matrix within cells,the cytoskeleton,and that which surrounds cells,the extracellular matrix（ECM）,are connected to one another through a number of receptors including those in primary cilia,serving as an important chemical and physical signaling system：Mechanical forces generated through the matrix play a critical role in determining the form and function of tissues（Hughes et al.,2018）.展开更多
The extracellular matrix is a diverse composition of glycoproteins and proteoglycans found in all cellular systems. The extracellular matrix, abundant in the mammalian central nervous system, is temporally and spatial...The extracellular matrix is a diverse composition of glycoproteins and proteoglycans found in all cellular systems. The extracellular matrix, abundant in the mammalian central nervous system, is temporally and spatially regulated and is a dynamic ＂living＂ entity that is reshaped and redesigned on a continuous basis in response to changing needs. Some modifications are adaptive and some are maladaptive. It is the maladaptive responses that pose a significant threat to successful axonal regeneration and/or sprouting following traumatic and spinal cord injuries, and has been the focus of a myriad of research laboratories for many years. This review focuses largely on the extracellular matrix component, chondroitin sulfate proteoglycans, with certain comparisons to heparan sulfate proteoglycans, which tend to serve opposite functions in the central nervous system. Although about equally as well characterized as some of the other proteoglycans such as hyaluronan and dermatan sulfate proteoglycan, chondroitin sulfate proteoglycans are the most widely researched and discussed proteoglycans in the field of axonal injury and regeneration. Four laboratories discuss various aspects of chondroitin sulfate proteoglycans and proteoglycans in general with respect to their structure and function （Beller and Snow）, the recent discovery of specific chondroitin sulfate proteoglycan receptors and what this may mean the field （Shen）, extracellular for increased advancements in matrix degradation by matrix metalloproteinases, which sculpt and resculpt to provide support for outgrowth, synapse formation, and synapse stability （Phillips et al.）, and the perilesion microenvironment with respect to immune system function in response to proteoglycans and central nervous system injuries （Jakeman et al.）.展开更多
Injury to central nervous system （CNS） tissues in adult mam- mals often leads to neuronal loss, scarring, and permanently lost neurologic functions, and this default healing response is increasingly linked to a pro-...Injury to central nervous system （CNS） tissues in adult mam- mals often leads to neuronal loss, scarring, and permanently lost neurologic functions, and this default healing response is increasingly linked to a pro-inflammatory innate immune response. Extracellular matrix （ECM） technology can reduce inflammation, while increasing functional tissue remodeling in various tissues and organs, including the CNS.展开更多
Regeneration in the central nervous system （CNS） is limited, and CNS damage often leads to cognitive impairment or permanent functional motor and sensory loss. Impaired regenerative capacity is multifactorial and in...Regeneration in the central nervous system （CNS） is limited, and CNS damage often leads to cognitive impairment or permanent functional motor and sensory loss. Impaired regenerative capacity is multifactorial and includes inflammation, loss of the blood-brain barrier, and alteration in the extracellular matrix （ECM）. One of the main problems is the formation of a glial scar and the production of inhibitory ECM, such as proteoglycans, that generates a physical and mechanical barrier, impeding axonal regrowth （Figure 1A）.展开更多
富含半胱氨酸的酸性分泌蛋白(secreted protein acidic and rich in cysteine, SPARC)是肿瘤微环境中重要的基质成分,它作为正常细胞恶变和肿瘤发生发展过程中一个重要的分子,能够调节多种肿瘤相关细胞因子及其受体的相互作用,并调节多...富含半胱氨酸的酸性分泌蛋白(secreted protein acidic and rich in cysteine, SPARC)是肿瘤微环境中重要的基质成分,它作为正常细胞恶变和肿瘤发生发展过程中一个重要的分子,能够调节多种肿瘤相关细胞因子及其受体的相互作用,并调节多种信号通路以及蛋白水解酶的表达水平。由于它抑制和促进肿瘤进展的能力取决于细胞类型、肿瘤分期等,因此在多种类型的肿瘤中差异表达,并可能成为肿瘤早期诊断的新型生物标记物以及治疗的新靶点。本文就近年来SPARC在肿瘤研究中的进展作一综述。展开更多
The regeneration of articular cartilage remains a great challenge due to the difficulty in effectively enhancing spontaneous healing.Recently,the combination of implanted stem cells,suitable biomaterials and bioactive...The regeneration of articular cartilage remains a great challenge due to the difficulty in effectively enhancing spontaneous healing.Recently,the combination of implanted stem cells,suitable biomaterials and bioactive molecules has attracted attention for tissue regeneration.In this study,a novel injectable nanocomposite was rationally designed as a sustained release platform for enhanced cartilage regeneration through integration of a chitosan-based hydrogel,articular cartilage stem cells(ACSCs)and mesoporous SiO_(2)nanoparticles loaded with anhydroicaritin(AHI).The biocompatible engineered nanocomposite acting as a novel 3D biomimetic extracellular matrix exhibited a remarkable sustained release effect due to the synergistic regulation of the organic hydrogel framework and mesopore channels of inorganic mSiO_(2)nanoparticles(mSiO_(2)NPs).Histological assessment and biomechanical tests showed that the nanocomposites exhibited superior performance in inducing ACSCs proliferation and differentiation in vitro and promoting extracellular matrix(ECM)production and cartilage regeneration in vivo.Such a novel multifunctional biocompatible platform was demonstrated to significantly enhance cartilage regeneration based on the sustained release of AHI,an efficient bioactive natural small molecule for ACSCs chondrogenesis,within the hybrid matrix of hydrogel and mSiO_(2)NPs.Hence,the injectable nanocomposite holds great promise for use as a 3D biomimetic extracellular matrix for tissue regeneration in clinical diagnostics.展开更多
基金supported by the Construction of Prevention and Treatment System of Geriatric Syndromes Focusing on Disability and Dementia(No.21-1-2-2-zyyd-nsh)。
文摘Objective This study aimed to explore the association of single nucleotide polymorphisms(SNP)in the matrix metalloproteinase 2(MMP-2)signaling pathway and the risk of vascular senescence(VS).Methods In this cross-sectional study,between May and November 2022,peripheral venous blood of151 VS patients(case group)and 233 volunteers(control group)were collected.Fourteen SNPs were identified in five genes encoding the components of the MMP-2 signaling pathway,assessed through carotid-femoral pulse wave velocity(cf PWV),and analyzed using multivariate logistic regression.The multigene influence on the risk of VS was assessed using multifactor dimensionality reduction(MDR)and generalized multifactor dimensionality regression(GMDR)modeling.Results Within the multivariate logistic regression models,four SNPs were screened to have significant associations with VS:chemokine(C-C motif)ligand 2(CCL2)rs4586,MMP2 rs14070,MMP2rs7201,and MMP2 rs1053605.Carriers of the T/C genotype of MMP2 rs14070 had a 2.17-fold increased risk of developing VS compared with those of the C/C genotype,and those of the T/T genotype had a19.375-fold increased risk.CCL2 rs4586 and MMP-2 rs14070 exhibited the most significant interactions.Conclusion CCL2 rs4586,MMP-2 rs14070,MMP-2 rs7201,and MMP-2 rs1053605 polymorphisms were significantly associated with the risk of VS.
基金This work was supported by a grant from Foundation of Education Department of China (NO.02190) and the Science and Technology Foundation of Guang-zhou City (NO.2002 Z1 -E0032)
文摘The effects of various cartilage extracellular matrix on the construction of rabbit growth plate cartilage tissue in vitro were studied. The results show that collagen, proteoglycan and hyaluronic acid can promote the growth of cultured chondrocytes but the effects of various cartilage extracellular matrix(ECM)on chondrocyte differentiation are different. Collagen can promote the hypertrophy of chondrocytes while proteoglycan and hyaluronic acid inhibit the transition of mature chondrocytes into hypertrophied chondrocytes.
基金Shanghai Municipal Natural Science Foundation,China(No.15ZR1400500)the Fundamental Research Funds for the Central Universities,China(Nos.16D110520,EG2017011)
文摘Extracellular matrix( ECM) plays a prominent role in establishing and maintaining an appropriate microenvironment for tissue regeneration. The aims of this study were to construct a tissue engineered scaffold by reconstituting osteoblast cell-derived ECM( O-ECM) on the electrospun nanofibrous scaffold,and further to evaluate its subsequent application for promoting the proliferation of bone marrow mesenchymal stem cells( BMSCs). To engineer a biomimetic scaffold, calvarial osteoblasts and electrospun poly-llactic acid( PLLA) nanofibers were prepared and subjected to decellularize for O-ECM deposition. To evaluate and characterize the O-ECM/PLLA scaffold, the morphology was examined and several specific mark proteins of osteoblasts matrix were evaluated.Furthermore,the cell counting kit-8( CCK-8) assay was used to detect the proliferation of the BMSCs cultivated on the O-ECM/PLLA scaffold. The results indicated O-ECM/PLLA scaffold was loaded with Collagen I, Fibronectin, and Laminin, as the composition of the marrow ECM. After decellularization,O-ECM deposition was observed in O-ECM/PLLA scaffold. Moreover,the O-ECM/PLLA scaffold could significantly enhance the proliferation of BMSCs,suggesting better cytocompatibility compared to the other groups tested. Taken together,a biomimetic scaffold based on the joint use of O-ECM and PLLA biomaterials,which represents a promising approach to bone tissue engineering, facilitates the expansion of BMSCs in vitro.
基金supported by MEYS of the Czech Republic,No.LO1309
文摘Functional repair of injured tissue in the adult central nervous system （CNS） still remains a big challenge for current biomed- ical research and its upcoming clinical translation. The axonal regeneration of the adult CNS is generally low, and it is addi- tionally restricted after injury by the presence of inhibitory mol- ecules, generated by the glial scar.
文摘Matrix within cells,the cytoskeleton,and that which surrounds cells,the extracellular matrix（ECM）,are connected to one another through a number of receptors including those in primary cilia,serving as an important chemical and physical signaling system：Mechanical forces generated through the matrix play a critical role in determining the form and function of tissues（Hughes et al.,2018）.
文摘The extracellular matrix is a diverse composition of glycoproteins and proteoglycans found in all cellular systems. The extracellular matrix, abundant in the mammalian central nervous system, is temporally and spatially regulated and is a dynamic ＂living＂ entity that is reshaped and redesigned on a continuous basis in response to changing needs. Some modifications are adaptive and some are maladaptive. It is the maladaptive responses that pose a significant threat to successful axonal regeneration and/or sprouting following traumatic and spinal cord injuries, and has been the focus of a myriad of research laboratories for many years. This review focuses largely on the extracellular matrix component, chondroitin sulfate proteoglycans, with certain comparisons to heparan sulfate proteoglycans, which tend to serve opposite functions in the central nervous system. Although about equally as well characterized as some of the other proteoglycans such as hyaluronan and dermatan sulfate proteoglycan, chondroitin sulfate proteoglycans are the most widely researched and discussed proteoglycans in the field of axonal injury and regeneration. Four laboratories discuss various aspects of chondroitin sulfate proteoglycans and proteoglycans in general with respect to their structure and function （Beller and Snow）, the recent discovery of specific chondroitin sulfate proteoglycan receptors and what this may mean the field （Shen）, extracellular for increased advancements in matrix degradation by matrix metalloproteinases, which sculpt and resculpt to provide support for outgrowth, synapse formation, and synapse stability （Phillips et al.）, and the perilesion microenvironment with respect to immune system function in response to proteoglycans and central nervous system injuries （Jakeman et al.）.
文摘Injury to central nervous system （CNS） tissues in adult mam- mals often leads to neuronal loss, scarring, and permanently lost neurologic functions, and this default healing response is increasingly linked to a pro-inflammatory innate immune response. Extracellular matrix （ECM） technology can reduce inflammation, while increasing functional tissue remodeling in various tissues and organs, including the CNS.
文摘Regeneration in the central nervous system （CNS） is limited, and CNS damage often leads to cognitive impairment or permanent functional motor and sensory loss. Impaired regenerative capacity is multifactorial and includes inflammation, loss of the blood-brain barrier, and alteration in the extracellular matrix （ECM）. One of the main problems is the formation of a glial scar and the production of inhibitory ECM, such as proteoglycans, that generates a physical and mechanical barrier, impeding axonal regrowth （Figure 1A）.
文摘富含半胱氨酸的酸性分泌蛋白(secreted protein acidic and rich in cysteine, SPARC)是肿瘤微环境中重要的基质成分,它作为正常细胞恶变和肿瘤发生发展过程中一个重要的分子,能够调节多种肿瘤相关细胞因子及其受体的相互作用,并调节多种信号通路以及蛋白水解酶的表达水平。由于它抑制和促进肿瘤进展的能力取决于细胞类型、肿瘤分期等,因此在多种类型的肿瘤中差异表达,并可能成为肿瘤早期诊断的新型生物标记物以及治疗的新靶点。本文就近年来SPARC在肿瘤研究中的进展作一综述。
基金supported by grants from The Ministry of Science and Technology of China(2020YFC2002800)the National Natural Science Foundation of China(81830078,21875044),NO.2021-NCRC-CXJJ-ZH-35 of Clinical Application-oriented Medical Innovation Foundation from National Clinical Research Center for Orthopedics,Sports Medicine&Rehabilitation and Jiangsu China-Israel Industrial Technical Research Institute Foundation,Sino-Swiss collaborative project from Ministry of Science and Technology(2015DFG32200)+1 种基金Science and Technology Commission of Shanghai Municipality(No.19XD1434100,19ZR1433100)Shanghai Jiaotong University“Cross research fund of Medical Engineering”(YG2019ZDA22).
文摘The regeneration of articular cartilage remains a great challenge due to the difficulty in effectively enhancing spontaneous healing.Recently,the combination of implanted stem cells,suitable biomaterials and bioactive molecules has attracted attention for tissue regeneration.In this study,a novel injectable nanocomposite was rationally designed as a sustained release platform for enhanced cartilage regeneration through integration of a chitosan-based hydrogel,articular cartilage stem cells(ACSCs)and mesoporous SiO_(2)nanoparticles loaded with anhydroicaritin(AHI).The biocompatible engineered nanocomposite acting as a novel 3D biomimetic extracellular matrix exhibited a remarkable sustained release effect due to the synergistic regulation of the organic hydrogel framework and mesopore channels of inorganic mSiO_(2)nanoparticles(mSiO_(2)NPs).Histological assessment and biomechanical tests showed that the nanocomposites exhibited superior performance in inducing ACSCs proliferation and differentiation in vitro and promoting extracellular matrix(ECM)production and cartilage regeneration in vivo.Such a novel multifunctional biocompatible platform was demonstrated to significantly enhance cartilage regeneration based on the sustained release of AHI,an efficient bioactive natural small molecule for ACSCs chondrogenesis,within the hybrid matrix of hydrogel and mSiO_(2)NPs.Hence,the injectable nanocomposite holds great promise for use as a 3D biomimetic extracellular matrix for tissue regeneration in clinical diagnostics.
