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Zeitschriftenartikel zum Thema "Extracellular matrix (ECM) peptides"
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Hozumi, Kentaro, und Motoyoshi Nomizu. „Mixed Peptide-Conjugated Chitosan Matrices as Multi-Receptor Targeted Cell-Adhesive Scaffolds“. International Journal of Molecular Sciences 19, Nr. 9 (11.09.2018): 2713. http://dx.doi.org/10.3390/ijms19092713.
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Biomaterials are important for cell and tissue engineering. Chitosan is widely used as a scaffold because it is easily modified using its amino groups, can easily form a matrix, is stable under physiological conditions, and is inactive for cell adhesion. Chitosan is an excellent platform for peptide ligands, especially cell adhesive peptides derived from extracellular matrix (ECM) proteins. ECM proteins, such as collagen, fibronectin, and laminin, are multifunctional and have diverse cell attachment sites. Various cell adhesive peptides have been identified from the ECM proteins, and these are useful to design functional biomaterials. The cell attachment activity of peptides is influenced by the solubility, conformation, and coating efficiency to solid materials, whereas immobilization of peptides to a polysaccharide such as chitosan avoids these problems. Peptide–chitosan matrices promote various biological activities depending on the peptide. When the peptides are immobilized to chitosan, the activity of the peptides is significantly enhanced. Further, mixed peptide–chitosan matrices, conjugated with more than one peptide on a chitosan matrix, interact with multiple cellular receptors and promote specific biological responses via receptor cross-talk. Receptor cross-talk is important for mimicking the biological activity of ECM and the proteins. The mixed peptide–chitosan matrix approach is useful to develop biomaterials as a synthetic ECM for cell and tissue engineering.
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Tran, Thi Xuan Thuy, Gyu-Min Sun, Hue Vy An Tran, Young Hun Jeong, Petr Slama, Young-Chae Chang, In-Jeong Lee und Jong-Young Kwak. „Synthetic Extracellular Matrix of Polyvinyl Alcohol Nanofibers for Three-Dimensional Cell Culture“. Journal of Functional Biomaterials 15, Nr. 9 (10.09.2024): 262. http://dx.doi.org/10.3390/jfb15090262.
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An ideal extracellular matrix (ECM) replacement scaffold in a three-dimensional cell (3D) culture should induce in vivo-like interactions between the ECM and cultured cells. Highly hydrophilic polyvinyl alcohol (PVA) nanofibers disintegrate upon contact with water, resulting in the loss of their fibrous morphology in cell cultures. This can be resolved by using chemical crosslinkers and post-crosslinking. A crosslinked, water-stable, porous, and optically transparent PVA nanofibrous membrane (NM) supports the 3D growth of various cell types. The binding of cells attached to the porous PVA NM is low, resulting in the aggregation of cultured cells in prolonged cultures. PVA NMs containing integrin-binding peptides of fibronectin and laminin were produced to retain the blended peptides as cell-binding substrates. These peptide-blended PVA NMs promote peptide-specific cell adherence and growth. Various cells, including epithelial cells, cultured on these PVA NMs form layers instead of cell aggregates and spheroids, and their growth patterns are similar to those of the cells cultured on an ECM-coated PVA NM. The peptide-retained PVA NMs are non-stimulatory to dendritic cells cultured on the membranes. These peptide-retaining PVA NMs can be used as an ECM replacement matrix by providing in vivo-like interactions between the matrix and cultured cells.
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Dolmatov, Igor Yu, und Vladimir A. Nizhnichenko. „Extracellular Matrix of Echinoderms“. Marine Drugs 21, Nr. 7 (22.07.2023): 417. http://dx.doi.org/10.3390/md21070417.
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This review considers available data on the composition of the extracellular matrix (ECM) in echinoderms. The connective tissue in these animals has a rather complex organization. It includes a wide range of structural ECM proteins, as well as various proteases and their inhibitors. Members of almost all major groups of collagens, various glycoproteins, and proteoglycans have been found in echinoderms. There are enzymes for the synthesis of structural proteins and their modification by polysaccharides. However, the ECM of echinoderms substantially differs from that of vertebrates by the lack of elastin, fibronectins, tenascins, and some other glycoproteins and proteoglycans. Echinoderms have a wide variety of proteinases, with serine, cysteine, aspartic, and metal peptidases identified among them. Their active centers have a typical structure and can break down various ECM molecules. Echinoderms are also distinguished by a wide range of proteinase inhibitors. The complex ECM structure and the variety of intermolecular interactions evidently explain the complexity of the mechanisms responsible for variations in the mechanical properties of connective tissue in echinoderms. These mechanisms probably depend not only on the number of cross-links between the molecules, but also on the composition of ECM and the properties of its proteins.
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Monteiro-Lobato, Gabriela M., Pedro S. T. Russo, Flavia V. Winck und Luiz H. Catalani. „Proteomic Analysis of Decellularized Extracellular Matrix: Achieving a Competent Biomaterial for Osteogenesis“. BioMed Research International 2022 (11.10.2022): 1–18. http://dx.doi.org/10.1155/2022/6884370.
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Decellularized ECMs have been used as biological scaffolds for tissue repair due to their tissue-specific biochemical and mechanical composition, poorly simulated by other materials. It is used as patches and powders, and it could be further processed via enzymatic digestion under acidic conditions using pepsin. However, part of the bioactivity is lost during the digestion process due to protein denaturation. Here, stepwise digestion was developed to prepare a competent biomaterial for osteogenesis from three different ECM sources. In addition, three different proteases were compared to evaluate the most effective digestion protocol for specific cellular processes. GAGs and peptide quantification showed that the stepwise method yielded a higher concentration of bioactive residues. Circular dichroism analysis also showed that the stepwise approach preserved the secondary structures better. The protein profiles of the digested ECMs were analyzed, and it was found to be highly diverse and tissue-specific. The digestion of ECM from pericardium produced peptides originated from 94 different proteins, followed by 48 proteins in ECM from tendon and 35 proteins in ECM from bone. In addition, digested products from pericardium ECM yielded increased proliferation and differentiation of bone marrow mesenchymal stem cells to mature osteoblasts.
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Fujita, Motomichi, Manabu Sasada, Takuya Iyoda, Satoshi Osada, Hiroaki Kodama und Fumio Fukai. „Biofunctional Peptide FNIII14: Therapeutic Potential“. Encyclopedia 1, Nr. 2 (08.04.2021): 350–59. http://dx.doi.org/10.3390/encyclopedia1020029.
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Biofunctional peptide FNIII14, which is derived from the 14th fibronectin (FN) type III-like (FN-III) repeat of FN molecule, is capable of inhibiting cell adhesion to the extracellular matrix (ECM). This functional site is usually buried within the molecular structure of FN, but can be exposed by conformational changes and proteolytic cleavage. Peptide FNIII14 can induce a conformational change in β1-integrin from the active to the inactive form, causing functional inactivation. Based on this anti-adhesive activity, peptide FNIII14 exhibits therapeutic potential for several diseases such as metabolic diseases, organ fibrosis, and malignant tumors. Peptide FNIII14 blocks integrin-mediated signaling by a mechanism entirely distinct from that of conventional antagonisitic peptides, including Arg-Gly-Asp peptides that competitively inhibit the ECM binding of integrin.
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Olivares-Navarrete, Rene, Sharon L. Hyzy, Argelia Almaguer-Flores, Corinna Mauth, Anja C. Gemperli, Barbara D. Boyan und Zvi Schwartz. „Amelogenin Peptide Extract Increases Differentiation and Angiogenic and Local Factor Production and Inhibits Apoptosis in Human Osteoblasts“. ISRN Biomaterials 2013 (01.08.2013): 1–11. http://dx.doi.org/10.5402/2013/347318.
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Enamel matrix derivative (EMD), a decellularized porcine extracellular matrix (ECM), is used clinically in periodontal tissue regeneration. Amelogenin, EMD’s principal component, spontaneously assembles into nanospheres in vivo, forming an ECM complex that releases proteolytically cleaved peptides. However, the role of amelogenin or amelogenin peptides in mediating osteoblast response to EMD is not clear. Human MG63 osteoblast-like cells or normal human osteoblasts were treated with recombinant human amelogenin or a 5 kDa tyrosine-rich amelogenin peptide (TRAP) isolated from EMD and the effect on osteogenesis, local factor production, and apoptosis assessed. Treated MG63 cells increased alkaline phosphatase specific activity and levels of osteocalcin, osteoprotegerin, prostaglandin E2, and active/latent TGF-β1, an effect sensitive to the effector and concentration. Primary osteoblasts exhibited similar, but less robust, effects. TRAP-rich 5 kDa peptides yielded more mineralization than rhAmelogenin in osteoblasts in vitro. Both amelogenin and 5 kDa peptides protected MG63s from chelerythrine-induced apoptosis. The data suggest that the 5 kDa TRAP-rich sequence is an active amelogenin peptide that regulates osteoblast differentiation and local factor production and prevents osteoblast apoptosis.
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Merchant, Michael L., Michelle T. Barati, Dawn J. Caster, Jessica L. Hata, Liliane Hobeika, Susan Coventry, Michael E. Brier et al. „Proteomic Analysis Identifies Distinct Glomerular Extracellular Matrix in Collapsing Focal Segmental Glomerulosclerosis“. Journal of the American Society of Nephrology 31, Nr. 8 (19.06.2020): 1883–904. http://dx.doi.org/10.1681/asn.2019070696.
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BackgroundThe mechanisms leading to extracellular matrix (ECM) replacement of areas of glomerular capillaries in histologic variants of FSGS are unknown. This study used proteomics to test the hypothesis that glomerular ECM composition in collapsing FSGS (cFSGS) differs from that of other variants.MethodsECM proteins in glomeruli from biopsy specimens of patients with FSGS not otherwise specified (FSGS-NOS) or cFSGS and from normal controls were distinguished and quantified using mass spectrometry, verified and localized using immunohistochemistry (IHC) and confocal microscopy, and assessed for gene expression. The analysis also quantified urinary excretion of ECM proteins and peptides.ResultsOf 58 ECM proteins that differed in abundance between cFSGS and FSGS-NOS, 41 were more abundant in cFSGS and 17 in FSGS-NOS. IHC showed that glomerular tuft staining for cathepsin B, cathepsin C, and annexin A3 in cFSGS was significantly greater than in other FSGS variants, in minimal change disease, or in membranous nephropathy. Annexin A3 colocalized with cathepsin B and C, claudin-1, phosphorylated ERK1/2, and CD44, but not with synaptopodin, in parietal epithelial cells (PECs) infiltrating cFSGS glomeruli. Transcripts for cathepsins B and C were increased in FSGS glomeruli compared with normal controls, and urinary excretion of both cathepsins was significantly greater in cFSGS compared with FSGS-NOS. Urinary excretion of ECM-derived peptides was enhanced in cFSGS, although in silico analysis did not identify enhanced excretion of peptides derived from cathepsin B or C.ConclusionsECM differences suggest that glomerular sclerosis in cFSGS differs from that in other FSGS variants. Infiltration of activated PECs may disrupt ECM remodeling in cFSGS. These cells and their cathepsins may be therapeutic targets.
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Barnes, Ashlynn M., Tessa B. Holmstoen, Andrew J. Bonham und Teisha J. Rowland. „Differentiating Human Pluripotent Stem Cells to Cardiomyocytes Using Purified Extracellular Matrix Proteins“. Bioengineering 9, Nr. 12 (22.11.2022): 720. http://dx.doi.org/10.3390/bioengineering9120720.
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Human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs) can be differentiated into cardiomyocytes (hESC-CMs and iPSC-CMs, respectively), which hold great promise for cardiac regenerative medicine and disease modeling efforts. However, the most widely employed differentiation protocols require undefined substrates that are derived from xenogeneic (animal) products, contaminating resultant hESC- and iPSC-CM cultures with xenogeneic proteins and limiting their clinical applicability. Additionally, typical hESC- and iPSC-CM protocols produce CMs that are significantly contaminated by non-CMs and that are immature, requiring lengthy maturation procedures. In this review, we will summarize recent studies that have investigated the ability of purified extracellular matrix (ECM) proteins to support hESC- and iPSC-CM differentiation, with a focus on commercially available ECM proteins and coatings to make such protocols widely available to researchers. The most promising of the substrates reviewed here include laminin-521 with laminin-221 together or Synthemax (a synthetic vitronectin-based peptide coating), which both resulted in highly pure CM cultures. Future efforts are needed to determine whether combinations of specific purified ECM proteins or derived peptides could further improve CM maturation and culture times, and significantly improve hESC- and iPSC-CM differentiation protocols.
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Hulahan, Taylor S., Laura Spruill, Elizabeth N. Wallace, Yeonhee Park, Robert B. West, Jeffrey R. Marks, E. Shelley Hwang, Richard R. Drake und Peggi M. Angel. „Extracellular Microenvironment Alterations in Ductal Carcinoma In Situ and Invasive Breast Cancer Pathologies by Multiplexed Spatial Proteomics“. International Journal of Molecular Sciences 25, Nr. 12 (19.06.2024): 6748. http://dx.doi.org/10.3390/ijms25126748.
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Ductal carcinoma in situ (DCIS) is a heterogeneous breast disease that remains challenging to treat due to its unpredictable progression to invasive breast cancer (IBC). Contemporary literature has become increasingly focused on extracellular matrix (ECM) alterations with breast cancer progression. However, the spatial regulation of the ECM proteome in DCIS has yet to be investigated in relation to IBC. We hypothesized that DCIS and IBC present distinct ECM proteomes that could discriminate between these pathologies. Tissue sections of pure DCIS, mixed DCIS-IBC, or pure IBC (n = 22) with detailed pathological annotations were investigated by multiplexed spatial proteomics. Across tissues, 1,005 ECM peptides were detected in pathologically annotated regions and their surrounding extracellular microenvironments. A comparison of DCIS to IBC pathologies demonstrated 43 significantly altered ECM peptides. Notably, eight fibrillar collagen peptides could distinguish with high specificity and sensitivity between DCIS and IBC. Lesion-targeted proteomic imaging revealed heterogeneity of the ECM proteome surrounding individual DCIS lesions. Multiplexed spatial proteomics reported an invasive cancer field effect, in which DCIS lesions in closer proximity to IBC shared a more similar ECM profile to IBC than distal counterparts. Defining the ECM proteomic microenvironment provides novel molecular insights relating to DCIS and IBC.
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Mazzocchi, Andrea, Kyung Min Yoo, Kylie G. Nairon, L. Madison Kirk, Elaheh Rahbar, Shay Soker und Aleksander Skardal. „Exploiting maleimide-functionalized hyaluronan hydrogels to test cellular responses to physical and biochemical stimuli“. Biomedical Materials 17, Nr. 2 (13.01.2022): 025001. http://dx.doi.org/10.1088/1748-605x/ac45eb.
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Abstract Current in vitro three-dimensional (3D) models of liver tissue have been limited by the inability to study the effects of specific extracellular matrix (ECM) components on cell phenotypes. This is in part due to limitations in the availability of chemical modifications appropriate for this purpose. For example, hyaluronic acid (HA), which is a natural ECM component within the liver, lacks key ECM motifs (e.g. arginine–glycine–aspartic acid (RGD) peptides) that support cell adhesion. However, the addition of maleimide (Mal) groups to HA could facilitate the conjugation of ECM biomimetic peptides with thiol-containing end groups. In this study, we characterized a new crosslinkable hydrogel (i.e. HA-Mal) that yielded a simplified ECM-mimicking microenvironment supportive of 3D liver cell culture. We then performed a series of experiments to assess the impact of physical and biochemical signaling in the form of RGD peptide incorporation and transforming growth factor ß (TGF-ß) supplementation, respectively, on hepatic functionality. Hepatic stellate cells (i.e. LX-2) exhibited increased cell–matrix interactions in the form of cell spreading and elongation within HA-Mal matrices containing RGD peptides, enabling physical adhesions, whereas hepatocyte-like cells (HepG2) had reduced albumin and urea production. We further exposed the encapsulated cells to soluble TGF-ß to elicit a fibrosis-like state. In the presence of TGF-ß biochemical signals, LX-2 cells became activated and HepG2 functionality significantly decreased in both RGD-containing and RGD-free hydrogels. Altogether, in this study we have developed a hydrogel biomaterial platform that allows for discrete manipulation of specific ECM motifs within the hydrogel to better understand the roles of cell–matrix interactions on cell phenotype and overall liver functionality.
Dissertationen zum Thema "Extracellular matrix (ECM) peptides"
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Maayouf, Hasna. „Développement de plateformes de signalisation dérivées de particules pseudo-virales pour contrôler les fonctions cellulaires“. Electronic Thesis or Diss., Mulhouse, 2024. http://www.theses.fr/2024MULH7387.
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Diverses stratégies de fonctionnalisation de surface visent à améliorer la biocompatibilité des matériaux pour les dispositifs implantables, notamment en ingénierie tissulaire. Par exemple, le polydiméthylsiloxane (PDMS), bien qu’utilisé dans de nombreux domaines, présente des propriétés de surface défavorables à l’adhérence cellulaire. La fonctionnalisation par des protéines de la matrice extracellulaire (MEC) ou des peptides synthétiques dérivés de celles-ci permet d’améliorer l'adhérence des cellules. Bien que ces approches offrent certaines solutions, des défis tels que le coût de production et le contrôle de la présentation en 3D entravent leur manipulation. Pour répondre à ces défis, nous avons développé des particules pseudo-virales (VLPs) présentant des peptides bioactifs à leur surface. La protéine d’enveloppe CP3, dérivée du bactériophage à ARN AP205, a été modifiée génétiquement à ses extrémités N- et C-terminales pour produire des VLPs présentant des peptides d’adhésion (RGD et YIGSR) et ostéogéniques (BMP2). La bioactivité des VLPs a été testée sur du PDMS avec des cellules de myoblastes C2C12, montrant une stimulation de l'adhérence, de la migration, de la prolifération et de la différenciation cellulaires. Des VLPs hétéromériques co-exprimant les peptides RGD et YIGSR ou BMP2 ont montré une bioactivité combinée. Des comparaisons entre la fibronectine et les VLP-RGD ont révélé des similarités et des différences dans les interactions cellulaires et la formation des adhésions focales. Ces résultats démontrent que les VLPs d’AP205 peuvent servir de nano-plateformes de signalisation, avec des applications potentielles en nanomédecine et dans les biomatériauxScientists have explored various surface functionalization strategies to improve the biocompatibility of materials used in implantable devices, particularly in tissue engineering. For example, polydimethylsiloxane (PDMS), although used in many fields, has surface properties that are unfavorable for cell adhesion. Functionalization with extracellular matrix (ECM) proteins or synthetic peptides derived from ECM components improves cell adhesion. While these approaches offer some solutions, challenges such as production cost and control over 3D presentation limit their use. To overcome these challenges, we developed virus-like particles (VLPs) displaying bioactive peptides on their surface. The coat protein CP3, derived from the RNA bacteriophage AP205, was genetically modified at both its N- and C-termini to produce VLPs displaying adhesion peptides (RGD and YIGSR) and an osteogenic peptide (BMP2). The bioactivity of the VLPs was tested on PDMS with C2C12 myoblast cells, demonstrating enhanced cell adhesion, migration, proliferation, and differentiation. Heteromeric VLPs co-expressing RGD and YIGSR or BMP2 peptides showed combined bioactivity. By comparing focal adhesions formed by RGD VLPs and those formed by fibronectin, we elucidate both the similarities and the differences in cell interactions. These results demonstrate that AP205 VLPs can be used as nanoscale signaling platforms to stimulate multiple cell functions, with promising applications in nanomedicine and biomaterials
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Kammerer, Theresa Anne [Verfasser], und Sebastian Johannes [Akademischer Betreuer] Arnold. „Visualization of the Extracellular Matrix (ECM) by fluorescent tagging of ECM components in mouse“. Freiburg : Universität, 2021. http://d-nb.info/1232644803/34.
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Randles, Michael. „Proteomic analyses of kidney glomerular extracellular matrix in health and disease“. Thesis, University of Manchester, 2015. https://www.research.manchester.ac.uk/portal/en/theses/proteomic-analyses-of-kidney-glomerular-extracellular-matrix-in-health-and-disease(a39fe408-db06-4d80-b97b-4e0651bf7bc3).html.
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Glomerular filtration is a vital physiological process removing waste products from the circulation and this process occurs across the glomerular filtration barrier (GFB). The cells and extracellular matrix (ECM), which form this barrier, are exposed to forces during ultrafiltration and special adaptation is required to withstand these forces. Dysfunction in cellular adhesion machinery or ECM assembly within the GFB causes loss of selective glomerular filtration, however, the mechanisms governing these processes are poorly understood. To this end we sought to characterise the glomerular ECM and adhesion machinery using high throughput mass spectrometry (MS)-based proteomics. MS of human glomerular ECM identified a highly complex extracellular niche, revealing the potential involvement of novel ECM proteins in glomerular development and disease processes. Furthermore we identified that glomerular cells in culture had distinct ECM proteomes and interestingly, coculture experiments demonstrated that the ECM proteome was influenced by cellular crosstalk and had a closer resemblance to glomerular ECM in vivo. Protein network analyses of in vivo and in vitro ECM datasets revealed a common core of highly connected structural ECM proteins that may be important for glomerular ECM assembly. To understand how this ECM proteome altered in disease, we studied mice with mild glomerular dysfunction. Here, transcriptomic and proteomic analyses identified alterations in ECM composition and 3D electron microscopy revealed striking ultrastructural changes in glomerular ECM. MS-based proteomics was next applied to the analysis of glomerular podocyte adhesion complexes, leading to the discovery that the actin cytoskeletal regulators and trafficking machinery are recruited to adhesions sites in an ECM-ligand dependent manner. Furthermore, these differences functionally altered cell shape and adhesion strength. These same analyses were applied to podocyte cell-cell junctions, revealing an unexpected overlap of cell-ECM and cell-cell adhesion machinery. Overall, these findings demonstrate for the first time the complexity of the glomerular ECM and adhesion signalling complexes and reinforce the benefits of global, unbiased experimental approaches. In addition the results suggest that glomerular ECM composition, organisation and adhesion signalling are context dependent, and therefore, represent potential therapeutic targets.
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Marengo, Kaitlyn A. „The Incorporation of Decellularized Cardiac ECM into Fibrin Microthreads“. Digital WPI, 2017. https://digitalcommons.wpi.edu/etd-theses/843.
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Stem cell therapies have shown promising capabilities in regaining the functionality of scar tissue following a myocardial infarction. Biological sutures composed of fibrin have been shown to more effectively deliver human mesenchymal stem cells (hMSCs) to the heart when compared to traditional cell delivery mechanisms. While the biological sutures do show promise, improvements can be made. To enhance the fibrin sutures, we propose to incorporate native cardiac extracellular matrix (ECM) into the fibrin microthreads to produce a more in vivo-like environment. This project investigated the effects that ECM incorporation has on fibrin microthread structure, mechanics, stem cell seeding, and pro-angiogenic potential. Single microthreads composed of fibrin or fibrin and ECM were subjected to uniaxial tensile testing. It was found that the microthreads consisting of both fibrin and ECM had significantly high elastic moduli than fibrin only microthreads. Cell seeding potential was evaluated by performing a 24-hour hMSC seeding experiment using sutures of the varying microthread types. A CyQuant cell proliferation assay was used to determine the number of cells seeded onto each suture type. The results determined that there was no statistical difference between the numbers of cells seeded on the types of sutures. To examine the pro-angiogenic potential the microthreads had, a 24-hour endothelial progenitor outgrowth cell (EPOC) outgrowth assay was used. Fibrin and 15% ECM-fibrin microthreads were placed within the scratch of an EPOC culture and evaluated every 6 hours for 24 hours. We found that the 15% ECM microthreads had significantly increased the EPOC outgrowth, approximately 16% more distance travelled than fibrin microthreads and 18% more than no microthreads. Our combined results suggest that ECM does not affect hMSC attachment to biological sutures but does increase the pro-angiogenic potential of the microthreads due to their increase in guiding EPOC outgrowth.
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Villaggio, Giusy. „Relationship between extracellular matrix (ECM) components and mineralization in bone marrow stromal cells“. Doctoral thesis, Università di Catania, 2014. http://hdl.handle.net/10761/1492.
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The relations between cells and extracellular matrix seem to orchestrate tissue organization by regulating cell functions during fetal development and throughout normal adult life. Thus, focusing on the innate ability of the native ECM to better modulate cell behavior, the coating of synthetic biomaterials with cell-derived decellularized extracellular matrices is a promising approach to confer bioactivity to inert materials and direct the fate of host or transplanted cells in tissue engineering applications.
This study aims to better understand ECM influence on human bone marrow stem cells and its role during the induction of an osteogenic phenotype. For this purpose decellularized matrices were prepared and examined for viability, morphology, adhesion, ALP content, mineralization and gene expression.
Extracellular matrix coatings were able to delay, unlike uncoated surfaces, cell spontaneous differentiation, underlying its role in the preservation of cell stemness. Furthermore, the combination of free cell ECM with osteogenic medium resulted in a strong effect on cell differentiation.
In conclusion, the ECM provides an ideal environment that promote cell adhesion and proliferation creating an ideal setting for the large-scale expansion of MSCs. In addition, it could enhance, in the presence of osteogenic factors, the cells differentiative ability providing the basis for an easier tissue-specific fate control of MSCs for therapeutic applications.
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Kwak, Hyo Bum. „Exercise training regulation of extracellular matrix and remodeling in the aging rat heart“. [College Station, Tex. : Texas A&M University, 2008. http://hdl.handle.net/1969.1/ETD-TAMU-2761.
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McKenna, Declan Joseph. „Studies of the 67 kilodalton laminin receptor in retinal vasculature“. Thesis, Queen's University Belfast, 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.300777.
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Singh, Mahipal, Cerrone R. Foster, Suman Dalal und Krishna Singh. „Osteopontin: Role in Extracellular Matrix Deposition and Myocardial Remodeling Post-MI“. Digital Commons @ East Tennessee State University, 2010. https://dc.etsu.edu/etsu-works/8576.
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Remodeling after myocardial infarction (MI) associates with left ventricular (LV) dilation, decreased cardiac function and increased mortality. The dynamic synthesis and breakdown of extracellular matrix (ECM) proteins play a significant role in myocardial remodeling post-MI. Expression of osteopontin (OPN) increases in the heart post-MI. Evidence has been provided that lack of OPN induces LV dilation which associates with decreased collagen synthesis and deposition. Inhibition of matrix metalloproteinases, key players in ECM remodeling process post-MI, increased ECM deposition (fibrosis) and improved LV function in mice lacking OPN after MI. This review summarizes — 1) signaling pathways leading to increased expression of OPN in the heart; 2) the alterations in the structure and function of the heart post-MI in mice lacking OPN; and 3) mechanisms involved in OPN-mediated ECM remodeling post-MI.
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Brian, Irene. „Crosstalk between ECM mechanical cues and cellular metabolism“. Doctoral thesis, Università degli studi di Padova, 2019. http://hdl.handle.net/11577/3422721.
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Mechanical cues coming from the extracellular matrix (ECM) are key factors in the control of tissue homeostasis in physiology and disease. Cells can sense these physical cues and measure external resisting forces by adjusting their actomyosin cytoskeleton, which in turn regulates intracellular signalling pathways to orchestrate a proper cell response. Thus, ECM stiffness is important for many biological aspects such as proliferation, differentiation and migration. Very little is known instead, about its impact on cellular metabolism, and the molecular players involved in this process are largely unknown. Starting from an unbiased metabolomics approach, we found lipid accumulation as a general response to mechanical signals and to low tension conditions. Mechanicistically, this accumulation is associated with a decreased Lipin1 phosphatidate phosphatase localization at ER/Golgi membranes and decreased Lipin1 activity which ultimately lead to nuclear translocation and activation of SREBP1/2 transcription factors. This occurs independently of YAP/TAZ and mTOR, and in parallel to the feedback control by sterols. Led by our findings, we discovered a coherent regulation of SREBP in stiffened pathological human tissues, and identified SREBP as required for the pro-survival activity of ROCK inhibitors in embryonic stem cells. We thus propose that SREBP is a general mechanism that links the physical cell microenvironment to a key metabolic pathwayGli stimoli meccanici provenienti dalla matrice extracellulare (ECM) sono fattori chiave nel controllo dell'omeostasi tissutale in condizioni fisiologiche e patologiche. Le cellule possono percepire questi segnali fisici e misurare le forze di resistenza esterne regolando il loro citoscheletro attraverso i filamenti di actomiosina, che a loro volta regolano le vie di segnalazione intracellulare per indurre una risposta cellulare adeguata. Pertanto, la rigidità della matrice extracellulare è importante per molti aspetti biologici come la proliferazione, la differenziazione e la migrazione. Si sa invece molto poco sull’ impatto che essa ha sul metabolismo cellulare, e i fattori molecolari coinvolti in questo processo sono in gran parte sconosciuti. Attraverso un’analisi metabolomica iniziale, abbiamo visto che le cellule tendono ad accumulare lipidi come risposta generale ai segnali meccanici e alle condizioni di bassa tensione. Abbiamo inoltre osservato che questo accumulo è associato ad un cambio di localizzazione della fosfatasi Lipin1, che diminuisce la sua affinità per le membrane del reticolo endoplasmatico e dell’apparato di Golgi e alla ridotta attività di Lipin1 che alla fine porta alla traslocazione nucleare e all'attivazione dei fattori di trascrizione SREBP1 / 2. Ciò si verifica indipendentemente dall’attività di YAP / TAZ e mTOR e in modo parallelo rispetto alla regolazione dei livelli di steroli nella cellula. Cercando una rilevanza biologica per il meccanisco da noi descritto, abbiamo inoltre scoperto che SREBP viene regolato in maniera coerente nei cheloidi, una patologia fibro-proliferativa legata a stress meccanici, e abbiamo identificato SREBP come un fattore importante e richiesto per la sopravvivenza di cellule staminali embrionali mediata dall’inibizione di ROCK. Quindi riassumendo, il nostro modello vede l’inibizione di LIPIN1 e l’attivazione di SREBP come un meccanismo generale che collega le forze fisiche derivanti dal microambiente e il metabolismo cellulare
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Bilem, Ibrahim. „Micro-engineered substrates as bone extracellular matrix mimics“. Doctoral thesis, Université Laval, 2016. http://hdl.handle.net/20.500.11794/27329.
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Il est de plus en plus évident que la matrice extracellulaire (MEC), au-delà de sa fonction d’échafaudage cellulaire, génère des signaux de nature biochimique et biophysique jouant un rôle primordial au cours du processus de différenciation des cellules souches. A l’heure actuelle, plus de 15 différents facteurs extrinsèques (environnementaux), incluant l’organisation spatiale de la MEC, sa topographie, rigidité, porosité, biodégradabilité et chimie ont été identifiés comme modulateurs potentiels de la différenciation des cellules souches en lignées cellulaires spécialisées. Ainsi, il est plausible que l’intégration d’un biomatériau au sein de l’organisme dépendra largement de sa capacité à mimer les propriétés de la MEC du tissu à remplacer. Récemment, les techniques de micro-ingénierie ont émergé comme outil innovant pour découpler les différentes propriétés de la MEC et étudier l’impact individuel ou combiné de ces facteurs sur le comportement des cellules souches. De plus, ces techniques de microfabrication ont un intérêt particulier dans une perspective de reconstruction de la MEC dans tous ses aspects, in vitro. Dans ce projet de thèse, le concept de déconstruction/reconstruction de la complexité de la MEC a été appliqué pour récapituler, in vitro, plusieurs aspects inhérents à la MEC osseuse et explorer leurs effets individuels ou combinés sur la différenciation ostéoblastique des cellules souches mésenchymateuses (CSMs) humaines. Trois principales composantes ont été utilisées tout au long du projet : un matériau modèle (verre borosilicate), des séquences peptidiques mimétiques dérivées de la MEC naturelle, favorisant à la fois l’adhérence cellulaire (peptide RGD) et la différenciation ostéoblastique (peptide BMP-2) des CSMs prélevées de la moelle osseuse des patients. La première étude du projet consiste à greffer, d’une manière aléatoire, les peptides RGD et/ou BMP-2 sur la surface du matériau. Brièvement, nous avons développé trois types de matériaux bioactifs : matériaux fonctionnalisés avec le peptide RGD, matériaux fonctionnalisés avec le peptide BMP-2 et matériaux bi-fonctionnalisés avec les peptides RGD/BMP-2. La caractérisation physicochimique de ces matériaux a été réalisée en utilisant la spectrométrie photoélectrique à rayons X (XPS) pour évaluer la composition chimique de la surface, la microscopie à force atomique (AFM) pour évaluer la topographie de la surface et la microscopie à fluorescence pour confirmer la présence des peptides sur la surface et évaluer leur densité. L’objectif de cette étude est d’évaluer le potentiel individuel et synergétique de ces peptides à induire et contrôler la différentiation ostéoblastique des CSMs. Dans un premier temps, la caractérisation physicochimique nous a permis de confirmer l’immobilisation covalente des peptides sur la surface et de mesurer leur densité. En effet, la densité des peptides, mesurée sur les surfaces greffées uniquement avec le peptide RGD ou BMP-2, était de 1.8 ± 0.2 pmol/mm² et 2.2 ± 0.3 pmol/mm², respectivement. Cependant, sur les surfaces bifonctionnalisées, la densité de chaque peptide a diminué de presque la moitié, atteignant 0.7 ± 0.1 pmol/mm² pour le peptide RGD et 1 ± 0.1 pmol/mm² pour le peptide BMP-2. Ensuite, l’évaluation biologique des différents matériaux fonctionnalisés a clairement révélé que contrairement au peptide RGD, le peptide BMP-2 induit la différenciation ostéoblastique des CSMs. Cependant, le greffage simultané des peptides RGD/BMP-2 améliore significativement la différenciation des CSMs en ostéoblastes et cela malgré la diminution significative de la densité de chaque peptide sur les surfaces bi-fonctionnalisées, comparativement aux surfaces contenant qu’un seul peptide. Ces résultats montrent que les peptides RGD et BMP-2 peuvent engendrer un effet synergétique pour améliorer la différenciation ostéoblastique des CSMs. Le second chapitre de thèse vise à déterminer si la microstructuration de la surface des matériaux avec des ligands bioactifs améliore la différenciation ostéoblastique des CSMs. En effet, les peptides RGD et BMP-2 ont été greffés séparément sur la surface du matériau sous forme de micro-motifs de différentes formes mais de taille similaire. En se basant sur des précédents travaux de littérature – discutés dans le chapitre II – nous avons sélectionné trois différentes formes de motifs peptidiques (triangle, carré et rectangle) dont la surface est de 50 μm². Ces micromotifs ont été créées grâce à une technique assez répondue et facile à utiliser qui est la photolithographie. Les surfaces microstructurées ont été caractérisées avec l’interférométrie optique et la microscopie à fluorescence. Les résultats montrent que les micromotifs peptidiques ont à la fois la forme et les dimensions prédéfinies. In vitro, les résultats de différenciation cellulaire ont révélé que la distribution spatiale des ligands à l’échelle micrométrique joue un rôle très important dans l’engagement et la différenciation des CSMs en ostéoblastes. En effet, contrairement aux micromotifs peptidiques en forme de rectangles, les micromotifs triangulaires et carrés améliorent significativement l’expression des marqueurs ostéogéniques (Runx-2 et Ostéopontine) comparativement à la distribution aléatoire des peptides. Il est important de noter que ce profile d’expression des marqueurs biologiques a été observé que sur les matériaux fonctionnalisés avec le peptide BMP-2, tant dis que les matériaux fonctionnalisés avec le peptide RGD n’ont induit aucun effet spécifique sur la différenciation des CSMs et cela peu importe la forme des micromotifs peptidiques. En conclusion, cette étude a permis d’identifier un nouveau facteur extracellulaire capable de contrôler la différenciation des CSMs. De plus, nous avons démontré que la distribution spatiale des ligands à l’échelle micrométrique affecte le devenir des CSMs, dépendamment de la nature du principe actif. Finalement, la troisième étude de ce projet de thèse est une suite logique de l’étude 1 et 2, puisqu’elle consiste à greffer simultanément les peptides RGD et BMP-2 sous forme de micromotifs. En effet, ces surfaces ont été développées afin de bénéficier à la fois de l’effet synergétique des peptides RGD/BMP-2, observé dans l’étude 1 (facteur 1), et de l’effet de la distribution spatiale contrôlée des ligands, observé dans l’étude 2 (facteur 2). Les différents types de matériaux ont été caractérisés avec les mêmes techniques de caractérisation de surface mentionnées dans l’étude 2. Les résultats montrent clairement que les surfaces microstructurées sont très bien définies et correspondent à un damier de micromotifs RGD, intercalé par un damier de micromotifs BMP-2. L’évaluation de la différenciation des CSMs sur ces matériaux a révélé que la combinaison des facteurs 1 et 2 améliore significativement la différenciation des CSMs vers le lignage ostéoblastique, comparativement à l’exposition des CSMs à un seul facteur extracellulaire (1 ou 2). De plus, cette étude confirme les résultats obtenus dans l’étude 2, puisque les micromotifs triangulaires et carrés ont permis une meilleure différenciation cellulaire, comparativement aux micromotifs rectangulaires. Il est important de noter également que l’évaluation biologique des différentes surfaces biomimétiques a été réalisée dans un milieu de culture basal qui ne contient pas de facteurs ostéogéniques solubles, afin d’étudier d’une manière assez précise et fiable les interactions des CSMs avec les différents microenvironnements in vitro développés dans ce projet. En conclusion générale, les travaux effectués jusqu’à présent ont permis d’identifier deux aspects de la MEC qui influencent considérablement la différenciation ostéoblastique des CSMs. De plus, nous avons démontré que ces deux facteurs peuvent coopérer pour induire une meilleure différenciation cellulaire. Cela révèle clairement l’intérêt des techniques de micro-ingénierie pour une meilleure et plus profonde compréhension des mécanismes d’interactions des cellules souches avec leurs niches, ce qui permettra éventuellement de concevoir des produits d’ingénierie tissulaire sur-mesure. Mots clés : Microstructuration de la surface des matériaux, matrice extracellulaire biomimétique, peptides mimétiques, BMP-2, cellules souches, ostéogenèse.It is becoming increasingly appreciated that the role of extracellular matrix (ECM) extends beyond acting as scaffolds to providing biochemical and biophysical cues, which are critically important in regulating stem cell self-renewal and differentiation. To date, more than 15 different extrinsic (environmental) factors, including the matrix spatial organization, topography, stiffness, porosity, biodegradability and chemistry have been identified as potent regulators of stem cells specification into lineage-specific progenies. Thus, it is plausible that the behavior of biomaterials inside the human body will depend to a large extent on their ability to mimic ECM properties of the tissue to be replaced. Recently, nano- and microengineering methods have emerged as an innovative tool to dissect the individual role of ECM features and understand how each element regulates stem cell fate. In addition, such tools are believed to be useful in reconstructing complex tissue-like structures resembling the native ECM to better predict and control cellular functions. In the thesis project presented here, the concept of deconstructing and reconstructing the ECM complexity was applied to reproduce several aspects inherent to the bone ECM and harness their individual or combinatorial effect on directing human mesenchymal stem cells (hMSCs) differentiation towards the osteoblastic lineage. Three main components were used throughout this project: a model material (borosilicate glass), ECM derived peptides (adhesive RGD and osteoinductive BMP-2 mimetic peptides) and bone marrow derived hMSCs. All cell differentiation experiments were performed in the absence of soluble osteogenic factors in the medium in order to precisely assess the interplay between hMSCs and the different artificial matrices developed in the current study. First, RGD and/or BMP-2 peptides were covalently immobilized and randomly distributed on glass surfaces. The objective here was to investigate the effect of each peptide as well as their combination on regulating hMSCs osteogenic differentiation. The most important funding was that RGD and BMP-2 peptides can act synergistically to enhance hMSCs osteogenesis. Then, micropatterning technique (photolithography) was introduced to control the spatial distribution of RGD and BMP-2 at the micrometer scale. The peptides were grafted individually onto glass substrates, as specific micropatterns of varied shapes (triangular, square and rectangle geometries) but constant size (50 μm² per pattern). In this second part of the project, the focus was made on investigating the role of ligands presentation in a spatially controlled manner in directing hMSCs differentiation into osteoblasts. Herein, we demonstrated that the effect of microscale geometric cues on stem cell differentiation is peptide dependent. Finally, glass surfaces modified with combined and spatially distributed peptides were used as in vitro cell culture models to evaluate the interplay between RGD/BMP-2 crosstalk and microscale geometric cues in regulating stem cell fate. In this study, we revealed that the combination of several ECM cues (ligand crosstalk and geometric cues), instead of the action of individual cues further enhances hMSCs osteogenesis. Overall, our findings provide new insights into the role of single ECM features as well their cooperation in regulating hMSCs fate. Such studies would allow the reconstruction of stem cell microenvironment in all the aspects ex vivo, which may pave the way towards the development of clinically relevant tissue-engineered constructs. Keywords: Chemical micropatterning, bioactive surfaces, mimetic peptides, BMP-2, mesenchymal stem cells, stem-cell differentiation, stem-cell niche, osteogenesis.
Bücher zum Thema "Extracellular matrix (ECM) peptides"
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(Editor), Nathan P. Colowick, Nathan P. Kaplan (Editor) und Leon W. Cunningham (Editor), Hrsg. Structural and Contractile Proteins, Part E: Extracellular Matrix, Volume 145: Volume 145: Structural and Contractile Proteins Part E (Methods in Enzymology). Academic Press, 1987.
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Lennon, Rachel, und Neil Turner. The molecular basis of glomerular basement membrane disorders. Herausgegeben von Neil Turner. Oxford University Press, 2018. http://dx.doi.org/10.1093/med/9780199592548.003.0320_update_001.
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The glomerular basement membrane (GBM) is a condensed network of extracellular matrix molecules which provides a scaffold and niche to support the function of the overlying glomerular cells. Within the glomerulus, the GBM separates the fenestrated endothelial cells, which line capillary walls from the epithelial cells or podocytes, which cover the outer aspect of the capillaries. In common with basement membranes throughout the body, the GBM contains core components including collagen IV, laminins, nidogens, and heparan sulphate proteoglycans. However, specific isoforms of these proteins are required to maintain the integrity of the glomerular filtration barrier.Across the spectrum of glomerular disease there is alteration in glomerular extracellular matrix (ECM) and a number of histological patterns are recognized. The GBM can be thickened, expanded, split, and irregular; the mesangial matrix may be expanded and glomerulosclerosis represents a widespread accumulation of ECM proteins associated with loss of glomerular function. Whilst histological patterns may follow a sequence or provide diagnostic clues, there remains limited understanding about the mechanisms of ECM regulation and how this tight control is lost in glomerular disease. Monogenic disorders of the GBM including Alport and Pierson syndromes have highlighted the importance of both collagen IV and laminin isoforms and these observations provide important insights into mechanisms of glomerular disease.
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MacGrogan, Donal, José Maria Pérez-Pomares, Bill Chaudhry, José Luis de la Pompa und Deborah J. Henderson. From cushions to leaflets: morphogenesis of cardiac atrioventricular valves. Herausgegeben von José Maria Pérez-Pomares, Robert G. Kelly, Maurice van den Hoff, José Luis de la Pompa, David Sedmera, Cristina Basso und Deborah Henderson. Oxford University Press, 2018. http://dx.doi.org/10.1093/med/9780198757269.003.0017.
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At the looping stage of heart development, tissue patterning of myocardium and endocardium at the atrioventricular (AV) junction defines a morphogenic field competent to form valves that initially appear as protrusions of proteoglycan-rich extracellular matrix (ECM) called endocardial cushions (ECs) which are cellularized by an endocardial-mesenchymal transition (EMT). Cellular proliferation results in fusion of the major AV mesenchymal cushions and AV septation, whereas smaller cushions receive a supply from epicardially derived cells. These various sources of mesenchyme precursors give rise to most of the valve structures, leaflets, annuli, and supporting tension apparatus. During valve leaflet maturation, the ECM matrix accumulates collagen and elastin and assembles into a thin flexible fibrous structure, which is remarkably tough. Valve development is regulated by the cross-talk between developmental signalling pathways. Pathogenic mutations in a subset of developmentally important genes have been linked to valve disease, suggesting that developmental defects may underlie valve disease in adulthood.
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van der Vlag, Johan, und Jo H. M. Berden. The patient with systemic lupus erythematosus. Herausgegeben von Giuseppe Remuzzi. Oxford University Press, 2015. http://dx.doi.org/10.1093/med/9780199592548.003.0161.
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Systemic lupus erythematosus (SLE) is a systemic autoimmune disease with various clinical manifestations. The hallmark of SLE is the presence of antibodies against nuclear constituents, such as double-stranded (ds)DNA, histones, and nucleosomes. Local deposition of antinuclear antibodies in complex with nuclear autoantigens induces serious inflammatory conditions that can affect several tissues and organs, including the kidney.The levels of antinucleosome and anti-dsDNA antibodies seem to correlate with glomerulonephritis and these autoantibodies can often be detected years before the patient is diagnosed with SLE. Apoptotic debris is present in the extracellular matrix and circulation of patients with SLE due to an aberrant process of apoptosis and/or insufficient clearance of apoptotic cells and apoptotic debris. The non-cleared apoptotic debris in patients with SLE may lead to activation of both the innate (myeloid and plasmacytoid dendritic cells) and adaptive (T and B cells) immune system. In addition to the activation by apoptotic debris and immune complexes, the immune system in SLE may be deregulated at the level of (a) presentation of self-peptides by antigen-presenting cells, (b) selection processes for both B and T cells, and (c) regulatory processes of B- and T-cell responses. Lupus nephritis may be classified in different classes based on histological findings in renal biopsies. The chromatin-containing immune complexes deposit in the capillary filter, most likely due to the interaction of chromatin with the polysaccharide heparan sulphate. A decreased renal expression of the endonuclease DNaseI further contributes to the glomerular persistence of chromatin and the development of glomerulonephritis.Current treatment of lupus nephritis is not specific and aims to reduce the inflammatory response with general immunosuppressive therapies. However, research has revealed novel potential therapeutic candidates at the level of dendritic cells, B cells, and T cells.
Buchteile zum Thema "Extracellular matrix (ECM) peptides"
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Helm, Richard F., und Malcolm Potts. „Extracellular Matrix (ECM)“. In Ecology of Cyanobacteria II, 461–80. Dordrecht: Springer Netherlands, 2012. http://dx.doi.org/10.1007/978-94-007-3855-3_18.
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Proske, Uwe, David L. Morgan, Tamara Hew-Butler, Kevin G. Keenan, Roger M. Enoka, Sebastian Sixt, Josef Niebauer et al. „Extracellular Matrix (ECM)“. In Encyclopedia of Exercise Medicine in Health and Disease, 329–30. Berlin, Heidelberg: Springer Berlin Heidelberg, 2012. http://dx.doi.org/10.1007/978-3-540-29807-6_2389.
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Papanicolaou, Michael, und Thomas R. Cox. „Extracellular Matrix (ECM)“. In Encyclopedia of Molecular Pharmacology, 1–8. Cham: Springer International Publishing, 2020. http://dx.doi.org/10.1007/978-3-030-21573-6_5691-1.
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Papanicolaou, Michael, und Thomas R. Cox. „Extracellular Matrix (ECM)“. In Encyclopedia of Molecular Pharmacology, 643–50. Cham: Springer International Publishing, 2021. http://dx.doi.org/10.1007/978-3-030-57401-7_5691.
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Balasubramanian, Swarnalatha, Elizabeth M. Powell und Jennie B. Leach. „Investigating Cell-ECM Interactions and ECM Synthesis in Three-Dimensional Hydrogels“. In Extracellular Matrix, 101–9. New York, NY: Springer New York, 2014. http://dx.doi.org/10.1007/978-1-4939-2083-9_10.
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Hennen, Eva, und Andreas Faissner. „Modulation of Neural Stem Cell Expressed Extracellular Matrix (ECM) by Targeting Glycosyltransferases“. In Extracellular Matrix, 151–60. New York, NY: Springer New York, 2014. http://dx.doi.org/10.1007/978-1-4939-2083-9_13.
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Zhang, Xiaoming, und Michael P. Sarras. „ECM in Hydra Development and Regeneration“. In Extracellular Matrix in Development, 163–86. Berlin, Heidelberg: Springer Berlin Heidelberg, 2013. http://dx.doi.org/10.1007/978-3-642-35935-4_7.
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Caravà, Elena, Cristiana Marcozzi, Barbara Bartolini, Marcella Reguzzoni, Paola Moretto, Ilaria Caon, Evgenia Karousou, Alberto Passi und Manuela Viola. „Method for Studying ECM Expression: In Situ RT-PCR“. In The Extracellular Matrix, 21–31. New York, NY: Springer New York, 2019. http://dx.doi.org/10.1007/978-1-4939-9133-4_2.
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Ghorbani, Farnaz, Niyousha Davari, Chaozong Liu und Behafarid Ghalandari. „Advances in ECM Protein-Based Materials“. In Handbook of the Extracellular Matrix, 1–44. Cham: Springer International Publishing, 2023. http://dx.doi.org/10.1007/978-3-030-92090-6_11-1.
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Ghorbani, Farnaz, Niyousha Davari, Chaozong Liu und Behafarid Ghalandari. „Advances in ECM Protein-Based Materials“. In Handbook of the Extracellular Matrix, 193–236. Cham: Springer International Publishing, 2024. http://dx.doi.org/10.1007/978-3-031-56363-8_11.
Der volle Inhalt der QuelleKonferenzberichte zum Thema "Extracellular matrix (ECM) peptides"
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Almirall, L., J. Aznar-Salatti, I. Calopa, A. Ordinas und E. Bastida. „ADHESION OF TUMOR CELLS TO EXTRACELLULAR MATRIX IS MEDIATED BY FIBRONECTIN“. In XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1643207.
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Tumor cell (TC) vessel wall adhesion is thougth to occur at specific sites of exposed extracellular matrix (ECM).To determine the role of fibronectin (FN) in TC/ECM adhesion,we measured; 1)TC adhesion to intact cultured endothelial cell monolayers (EC) or their ECMs,with or without incubation with a polyclonal antibody (Ab) to human FN, or a monoclonal antibody (Mab) to the cell binding site of FN (3E3);2)TC adhesion to EC or their exposed ECMs incubated with specific peptides against bacteria adhesion sites (I 133-79) or the peptide GRGDSP contained in the cell binding sites of several adhesive proteins.TC adhesion was measured as number of 111In-labeled A-549 adenocarcinoma cellsxlO /disc. ECMs were exposed by removing the ECs with N2 flow or EGTA treatment.There was 5.5±1x10 A-549/ EC covered disc (Table). Treatment of ECs with the Abs or peptides had no effect on TC adhesion.TC adhesion to the two ECM preparation were 42 ± 12 and 55±10 respectively.(Table).Blockage of the FN adhesive site by either Ab inhibited TC adhesion (p < 0.01). In contrast,blockage of the bacteria-adhesion site or incubation with GRGDSP had not significant effects in TC adhesion. The table shows the results (mearv±SEM (* p < 0.01).We conclude that TC adhesion to ECM but not to ECs,is dependent upon FN.
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Rawal, Atul, Kristen L. Rhinehardt und Ram V. Mohan. „Mechanical Behavior of Collagen Mimetic Peptides Under Fraying Deformation via Molecular Dynamics“. In ASME 2019 International Mechanical Engineering Congress and Exposition. American Society of Mechanical Engineers, 2019. http://dx.doi.org/10.1115/imece2019-11492.
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Abstract Collagen is a pervasive, triple helical, extracellular matrix (ECM) protein, found in human body from skin and bones to blood vessels and lungs, making it biocompatible, biodegradable, capable of cell attachment, and relevant for applications in bio-polymers, tissue engineering and a plethora of other bio-medical fields. Natural collagen’s extraction from natural sources is time consuming, sometimes costly, and it is difficult to render, and could present undesired biological and pathogenic changes. Nanoscale collagen mimetic peptides (Synthetic Collagen), without the unwanted biological entities present in the medium, has shown to mimic the unique properties that are present in natural collagen. Synthetic collagen, thus provides a superior alternative compared to natural collagen for its utilization in several applications. Their properties are affected by surrounding environments, including various solvents, and can be tailored toward specific applications. The focus of this paper is to investigate the mechanical properties of these nanoscale collagen mimetic peptides with lengths of about 10nm, leading to understanding of their feasibility in bio-printing of a composite polymeric collagen biomaterial with a blend of multiple synthetic collagen molecules. Molecular dynamics modeling is used to simulate, model and analyze mechanical properties of synthetic collagen peptides. In particular, mechanical behavior of these peptides are studied. An in-depth insight into the deformation and structural properties of the collagen peptides are of innovative significance for a multitude of bio medical engineering applications. Present paper employed steered molecular dynamics as the principal method of investigating the mechanical properties of nanoscale collagen mimetic peptide 1BKV, which closely resembles natural collagen with a shorter sequence length of 30 amino acids. A detailed comprehension of the protein’s mechanical properties is investigated through fraying deformation behavior studied. A calculated Gibbs free energy value of 40 Kcal/mol corresponds with a complete unfolding of a single alpha-helix peptide chain from a triple helical protein in case of fraying. Force needed for complete separation of the alpha-helix from the triple-helical protein is analyzed, and discussed in this paper.
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Hurley, Jennifer R., und Daria A. Narmoneva. „Endothelial-Fibroblast Interactions in Angiogenesis and Matrix Remodeling“. In ASME 2009 Summer Bioengineering Conference. American Society of Mechanical Engineers, 2009. http://dx.doi.org/10.1115/sbc2009-206534.
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Revascularization is critical for successful regeneration of ischemic cardiac tissue after injury. To achieve revascularization in engineered cardiac grafts, it is necessary to understand the interactions between major cardiac cell types. The importance of cardiomyocyte-endothelial interactions in angiogenesis is well documented [1]; however, less is known about interactions between endothelial and stromal cells, fibroblasts in particular. Studies indicate that during capillary assembly, fibroblasts (FBs) provide chemical signaling via growth factor expression and endothelial activation and proliferation [2]. In addition, fibroblasts deposit extracellular matrix (ECM) proteins [3] and also play a role in matrix remodeling. The objective of our study was to further investigate the role of endothelial-fibroblast interactions in angiogenesis with a focus on FB regulation of the extracellular mechanical environment. We and others have recently shown that self-assembling peptide nanoscaffold is a promising material for cardiac tissue regeneration, enhancing angiogenesis in vitro and promoting tissue neovascularization in vivo [1, 4–5]. An important advantage of this nanoscaffold is the ability to control its material properties, such as stiffness and rate of MMP degradation, through its sequence and/or concentration [6]. In this study, RAD16-II peptide nanoscaffold was used as a controlled system to test the hypothesis that fibroblasts regulate angiogenesis via modifying the extracellular mechanical environment through mechanisms including cell-mediated scaffold disruption and matrix remodeling.
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Hurley, Jennifer R., Abdul Q. Sheikh, Meredith Beckenhaupt, Cameron Ingram, Andrew Mutchler und Daria A. Narmoneva. „Self-Assembling Peptide Nanofibers for MMP Delivery and Cardiac Regeneration in Diabetes“. In ASME 2011 Summer Bioengineering Conference. American Society of Mechanical Engineers, 2011. http://dx.doi.org/10.1115/sbc2011-53761.
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Diabetes is a serious problem in the United States, afflicting 7.8% of the population with annual medical costs estimated at $116B in 2007 (1). Diabetic cardiomyopathy (DCM) is a cardiovascular complication of diabetes resulting in pathological alterations to the myocardium including circulatory defects, impaired heart muscle contraction, and progressive fibrosis. Cardiac fibrosis is associated with an imbalance between the deposition of the extracellular matrix (ECM) proteins by cardiac fibroblasts and the ECM proteolytic degradation via matrix metalloproteinases (MMPs). Recent studies have demonstrated that in the diabetic heart, expression and activity of MMP-2 are reduced, resulting in increased collagen accumulation and cardiac dysfunction (2). These observations suggest that a MMP-related mechanism may contribute to cardiac fibrosis, and that it may be attenuated through stimulation of native MMP-2 expression or delivery of exogenous MMP-2. Therefore, reduced MMP-2 activity in DCM may represent a novel target for therapeutic treatment (3). To achieve this, a special proteolytically-stable delivery scaffold would be needed, because native ECM is rapidly degraded by MMPs. The goal of this study is to determine if self-assembling peptide nanofibers can be used for long-term (several weeks) MMP delivery and enhancement of cardiac remodeling. This study tests the hypothesis that increased MMP-2 concentration (native or exogenous) in the nanofiber environment will promote matrix remodeling in diabetic cardiac fibroblasts in vitro.
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Ciardelli, G., F. M. Montevecchi, P. Giusti, D. Silvestri, I. Morelli, C. Cristallini und G. Vozzi. „Molecular Imprinted Nanostructures in Biomedical Applications“. In ASME 8th Biennial Conference on Engineering Systems Design and Analysis. ASMEDC, 2006. http://dx.doi.org/10.1115/esda2006-95669.
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Molecular imprinting is an emerging technology that allows to introduce nanostructured cavities into a polymer. In preparing molecular imprinted polymers (MIPs), the functional monomer(s) is first prearranged around the template molecule by specific interactions; the polymerisation is then carried out with a high percentage of cross-linking agent (which “freezes” the macromolecular network). Molecular mechanics and dynamics can be used to gain indications on the best monomers to be used in order to maximize interactions with the template. Once the polymerization reaction has been completed, the template is removed from the rigid three-dimensional network, leaving free recognition cavities available for the successive selective rebinding of the template itself. Precipitation polymerisation in dilute solutions involves the spontaneous formation of submicron scale polymer particles, which result suitable for recognition-rebinding application. Therapeutic applications: The recognition mechanism by MIPs relies mainly on the establishment of reversible hydrogen bonding interactions. It is clear that the efficiency of this mechanism is endangered in aqueous environments. MIPs working in water solutions are clearly of great interest in the medical and food industry and in sensor applications. We recently overcame these difficulties by the realisation of a system where cross-linked MI methylmethacrylate-methacrylic acid nanospheres where loaded on the surface or inside the matrix of porous membranes created by phase inversion. E.g. membranes were modified by adding cholesterol imprinted nanoparticles. Rebinding performances of nanoparticles modified membranes in buffer solution were tested showing a specific recognition of 14.09 mg of cholesterol/g of system (membrane and nanoparticles), indicating maintained binding capacity of supported particles as well. Tissue engineering: The engineering of functionalised polymeric structures for the study of cell activity is essential to the development of biological substitutes containing vital cells capable of regenerating or enhancing tissue function. Cells are organised within a complex matrix consisting of high molecular weight protein and polysaccharides known as the Extracellular Matrix (ECM). Two approaches are described to explore the possibility to provide scaffolds with specific and selective recognition of peptide sequences or proteins involved in cell adhesion mechanisms: one approach consists in the modification of porous structures with nanoparticles imprinted with aminoacid sequences (epitopes) of ECM proteins or transmembrane integrins, while the other consists in the combination of Soft Litography and Molecular Imprinting technologies (SOFT-MI). This technology allows to create imprinting nanocavities selective towards ECM proteins in microfabricated scaffolds, and in particular it permits to realise patterns with a well defined microscale geometry in polymethylmethacrylate (PMMA) scaffolds providing them with cell adhesion properties that were missing in the non-imprinted scaffold.
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Freytes, Donald O., Samuel Kolman, Sachin S. Velankar und Stephen F. Badylak. „Rheological Properties of Extracellular Matrix Derived Gels“. In ASME 2007 Summer Bioengineering Conference. American Society of Mechanical Engineers, 2007. http://dx.doi.org/10.1115/sbc2007-176537.
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Bioscaffolds composed of extracellular matrix (ECM) have been used for the repair of a variety of tissues often leading to tissue-specific constructive remodeling [1]. ECM scaffolds are typically prepared by decellularization of tissues and are composed of the structural proteins (e.g. collagen) and functional proteins (e.g. growth factors) that characterize the native ECM. However, for certain applications, the use of ECM scaffolds can be limited by the native two-dimensional sheet form in which they are harvested.
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Kong, AKCW, JMB Sand, DJ Leeming, SR Rønnow, CM Spalluto, K. Staples, K. Ostridge, A. Platt und T. Wilkinson. „S62 Extracellular matrix (ECM) remodelling in COPD“. In British Thoracic Society Winter Meeting 2024, QEII Centre, Broad Sanctuary, Westminster, London SW1P 3EE, 27 to 29 November 2024, Programme and Abstracts, A48. BMJ Publishing Group Ltd and British Thoracic Society, 2024. http://dx.doi.org/10.1136/thorax-2024-btsabstracts.68.
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Roeder, Blayne A., Klod Kokini, Jennifer E. Sturgis, J. Paul Robinson und Sherry L. Voytik-Harbin. „Micromechanics of Extracellular Matrix: Three-Dimensional Microstructure Under Load“. In ASME 2001 International Mechanical Engineering Congress and Exposition. American Society of Mechanical Engineers, 2001. http://dx.doi.org/10.1115/imece2001/bed-23165.
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Abstract The extracellular matrix (ECM) guides tissue form and function by communicating to cells both biochemical and mechanical information about the local micro-environment. It is well established that mechanical loads to tissues influence fundamental cellular processes including proliferation, migration, formation of adhesion complexes, and gene expression [1]. However, the pathway that transduces these forces from the tissue (macro) to the cellular (micro) level remains to be elucidated. In order to understand how cells interact mechanically with their surroundings, the three-dimensional (3D) micromechanical properties of the ECM must be understood. Advancements in the knowledge of ECM micro-behavior will be key to the development of future tissue engineering strategies.
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Levine, R. F., A. Eldor, R. Stromberg, I. Vlodavsky, E. HyAm, A. R. Koslow und L. I. Friedman. „THE EFFECT OF FLOW ON THE INTERACTION OF ISOLATED MEGAKARYOCYTES WITH EXTRACELLULAR MATRIX“. In XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1644617.
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To examine the effect of flow on megakaryocytes (megas) exposed to extracellular matrix (ECM), we subjected megas on ECM to laminar flow in a chamber similar to that used to study platelets circulated over aortic subendothelium. Megas, harvested from guinea pig bone marrow by centrifugal elutriation and velocity sedimentation, were allowed to adhere to cover slips coated with ECM, which were then placed in a perfusion chamber. Medium was circulated over the megas on this surface for up to 18 hrs. The cells were examined during the experiments by phase contrast and afterwards by scanning electron microscopy. With time, many attached megas developed a single, prominent, elongated pseudopod resembling the flagelliform processes observed in situ protruding into marrow sinusoids and also observed in circulating megas. In other experiments megas were introduced into the flowing medium and exposed to new ECM-coated cover slips mounted in the chamber. At shear rates of 10-200 sec−1, megas from the flowing suspension started to adhere to the ECM within 1 to 2 minutes. The number of attached cells continued to increase for several hours. Adhesion of megas under flow to the ECM was specific, since there was no adherence to glass, to glutaraldehyde-fixed ECM coated cover slips or to endothelial cells cultured on ECM coated cover slips. With time many of the megas developed the same type of pseudopods which formed in megas attached to ECM prior to flow exposure. The responses of megas to flow over ECM illustrate two aspects of mega behavior: the acquisition, even before platelet shedding, of the adhesive capacity of circulating platelets, and the possible roles of ECM and flow as anchor and inducer of platelet shedding.
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Steward, Robert L., Chao-Min Cheng und Philip R. LeDuc. „Probing Dynamic Responses of the Extracellular Matrix to Coupled Mechanical and Chemical Inputs“. In ASME 2010 Summer Bioengineering Conference. American Society of Mechanical Engineers, 2010. http://dx.doi.org/10.1115/sbc2010-19206.
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The extracellular matrix (ECM) is an important cellular component that provides structural support for cells that form the various connective tissues in the body and has been linked to various important cellular processes. One major, ubiquitously expressed ECM protein, fibronectin (FN) has been well documented to play an important role in the ECM, but most studies have investigated FN and its assembly and structural organization mainly through chemical stimulation. The ECM though likely experiences multiple modes of stimulation such as mechanical and chemical inputs. Since cells and the ECM may experience mechanical and chemical stimulation, we examined how NIH 3T3 fibroblasts altered their ECM in response to applied mechanical and chemical stimulation. Mechanical stimulation revealed an increase in FN matrix formation and secretion as reflected by immunofluorescence as well as FN localization around the cell periphery. Coupling of mechanical stimulation with chemical stimulation via inhibition of Rho activity revealed the same behavior as cells exposed purely to mechanical stimulation. This study is among the first to show the effect of coupled modes of stimulation on the ECM and show a purely mechanics-induced stimulation of ECM formation. These results have implications in a variety of fields including mechanotransduction, biophysics and bioengineering.
Berichte der Organisationen zum Thema "Extracellular matrix (ECM) peptides"
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Barash, Itamar, J. Mina Bissell, Alexander Faerman und Moshe Shani. Modification of Milk Composition via Transgenesis: The Role of the Extracellular Matrix in Regulating Transgene Expression. United States Department of Agriculture, Juli 1995. http://dx.doi.org/10.32747/1995.7570558.bard.
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Altering milk composition via transgenesis depends on three main factors. (1) The availability of an efficient regulatory sequences for targeting transgene(s) to the mammary gland; (2) a reliable in vitro model to test the expression of transgenes prior to their introduction to the animal genome; and (3) better understanding of the major factors which determine the rate of gene expression and protein synthesis. The current studies provide the necessary means and knowledge to alter milk protein composition via transgenesis. The following specific goals were achieved: a: Identifying regulatory regions in the b-lactoglobulin (BLG) gene and the cross-talk between elements which enabled us to construct an efficient vector for the expression of desirable cDNA's in the mammary gland. b: The establishment of a sheep mammary cell line that serves as a model for the analysis of endogenous and exogenous milk protein synthesis in the mammary gland of livestock. c: An accurate comparison of the potency of the 5' regulatory sequences from the BLG and whey acidic protein (WAP) promoters in directing the expression of human serum albumin (HSA) to the mammary gland in vitro and in vivo. In this study we have also shown that sequences within the coding region may determine a specific pattern of expression for the transgene, distinct from that of the native milk protein genes. d: Characterizing the dominant role of ECM in transgene expression in mammary epithelial cells. e: Further characterization of the BCE-1 enhancer element in the promoter of the b-casein gene as a binding site for the c/EBP-b and Stat5. Identifying its interaction with chromatin and its up regulation by inhibitors of histone deacetylation. f: Identifying a mechanism of translational control as a mediator for the synergistic effect of insulin and prolactin on protein synthesis in the mammary gland.
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Cao, Siyang, Yihao Wei, Huihui Xu, Jian Weng, Tiantian Qi, Fei Yu, Su Liu, Ao Xiong, Peng Liu und Hui Zeng. Crosstalk between Ferroptosis and Chondrocytes in Osteoarthritis: A Systematic Review of in-vivo and in-vitro Studies. INPLASY - International Platform of Registered Systematic Review and Meta-analysis Protocols, März 2023. http://dx.doi.org/10.37766/inplasy2023.3.0044.
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Review question / Objective: For the sake of better apprehending the nexus between ferroptosis and chondrocytes in osteoarthritis (OA), proffering novel insights and opening-up new orientation for in-depth research in both pre-clinical and clinical settings, it is warranted to initiate one rigorous and robust systematic review (SR) based upon up-to-date in-vivo and in-vitro research advances on this topic. To the best our knowledge, no SRs concerning ferroptosis and chondrocytes in OA have been published thus far. Condition being studied: Osteoarthritis (OA) is the most common form of arthritis, which menaces 7% of the human population globally. With the aged tendency of population and higher rates of obesity, the incidence of OA is anticipated to proliferate, which will entail a mounting impact and major challenges for global health care and each country’s public health systems unavoidably. In virtue of the onset of OA is mighty knotty, its etiology and underlying molecular mechanisms have not been expressly expounded. However, the salient role that cartilage degeneration acts in the progression of OA has been widely acknowledged. Chondrocytes are consequential for the safeguard of cartilage homeostasis and the functional integrity of the articular cartilage. Once the homeostatic equilibrium of the extracellular matrix (ECM) synthesis and degradation is smashed, OA comes up.