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Artigos de revistas sobre o assunto "Proteoglycans Physiological effect"
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Hamati, H. F., E. L. Britton e D. J. Carey. "Inhibition of proteoglycan synthesis alters extracellular matrix deposition, proliferation, and cytoskeletal organization of rat aortic smooth muscle cells in culture." Journal of Cell Biology 108, n.º 6 (1 de junho de 1989): 2495–505. http://dx.doi.org/10.1083/jcb.108.6.2495.
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Arterial proteoglycans have been implicated in several important physiological processes ranging from lipid metabolism to regulation of smooth muscle cell growth. Vascular smooth muscle (VSM) cells are the major producers of proteoglycans in the medial layer of blood vessels. To study functional consequences of alterations in VSM proteoglycan metabolism we used 4-methylumbelliferyl-beta-D-xyloside to inhibit proteoglycan synthesis in primary and early passage cultures of rat aortic smooth muscle cells. Biochemical analysis of cultures labeled with 35SO4 showed the drug inhibited synthesis of different classes of proteoglycans by 50 to 62%. Inhibition of proteoglycan synthesis resulted in reduced accumulation of extracellular matrix, as shown by immunofluorescent staining with antibodies to chondroitin sulfate, fibronectin, thrombospondin, and laminin. There was also an inhibition of postconfluent (multilayered) growth of the smooth muscle cells, and a change in the morphology of the cells, with no apparent effect on subconfluent growth. In addition, in drug-treated cells there was a reduction in the number of cytoskeletal filaments that contained alpha-actin, the actin subtype synthesized by differentiated VSM cells. This occurred even though the total content of alpha-actin in the cells was not reduced. The effects of the inhibitor on growth and morphology could be reversed by switching the cultures to normal medium and could be prevented by growing the cells on preformed VSM extracellular matrix. These observations suggest the vascular extracellular matrix may play a role in regulating the growth and differentiation of smooth muscle cells.
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Sah, R. L. Y., A. J. Grodzinsky, A. H. K. Plaas e J. D. Sandy. "Effects of tissue compression on the hyaluronate-binding properties of newly synthesized proteoglycans in cartilage explants". Biochemical Journal 267, n.º 3 (1 de maio de 1990): 803–8. http://dx.doi.org/10.1042/bj2670803.
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The effects of tissue compression on the hyaluronate-binding properties of newly synthesized proteoglycans in calf cartilage explants were examined. Pulse-chase experiments showed that conversion of low-affinity monomers to the high-affinity form (that is, to a form capable of forming aggregates with 1.6% hyaluronate on Sephacryl S-1000) occurred with a t1/2 of about 5.7 h in free-swelling discs at pH 7.45. Static compression during chase (in pH 7.45 medium) slowed the conversion, as did incubation in acidic medium (without compression). Both effects were dose-dependent. For example, the t1/2 for conversion was increased to about 11 h by either (1) compression from a thickness of 1.25 mm to 0.5 mm or (2) medium acidification from pH 7.45 to 6.99. Oscillatory compression of 2% amplitude at 0.001, 0.01, or 0.1 cycles/s during chase did not, however, affect the conversion. Changes in the hyaluronate-binding affinity of [35S]proteoglycans in these experiments were accompanied by no marked change in the high percentage (approximately 80%) of monomers which could form aggregates with excess hyaluronate and link protein. Since static tissue compression would result in an increased matrix proteoglycan concentration and thereby a lower intra-tissue pH [Gray, Pizzanelli, Grodzinsky & Lee (1988) J. Orthop. Res. 6, 777-792], it seems likely that matrix pH may influence proteoglycan aggregate assembly by an effect on the hyaluronate-binding affinity of proteoglycan monomer. Such a pH mechanism might have a physiological role, promoting proteoglycan deposition in regions of low proteoglycan concentration.
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Kolb, Martin, Peter J. Margetts, Patricia J. Sime e Jack Gauldie. "Proteoglycans decorin and biglycan differentially modulate TGF-β-mediated fibrotic responses in the lung". American Journal of Physiology-Lung Cellular and Molecular Physiology 280, n.º 6 (1 de junho de 2001): L1327—L1334. http://dx.doi.org/10.1152/ajplung.2001.280.6.l1327.
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Transforming growth factor (TGF)-β is a key cytokine in the pathogenesis of pulmonary fibrosis, and pharmacological interference with TGF-β can ameliorate the fibrotic tissue response. The small proteoglycans decorin and biglycan are able to bind and inhibit TGF-β activity in vitro. Although decorin has anti-TGF-β properties in vivo, little is known about the physiological role of biglycan in vivo. Adenoviral gene transfer was used to overexpress active TGF-β, decorin, and biglycan in cell culture and in murine lungs. Both proteoglycans were able to interfere with TGF-β bioactivity in vitro in a dose-dependant manner. In vivo, overexpression of TGF-β resulted in marked lung fibrosis, which was significantly reduced by concomitant overexpression of decorin. Biglycan, however, had no significant effect on lung fibrosis induced by TGF-β. The data suggest that differences in tissue distribution are responsible for the different effects on TGF-β bioactivity in vivo, indicating that decorin, but not biglycan, has potential therapeutic value in fibrotic disorders of the lung.
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Schröer, Katrin, Montaha Alshawabkeh, Sebastian Schellhorn, Katrin Bronder, Wenli Zhang e Anja Ehrhardt. "Influence of Heparan Sulfate Proteoglycans and Factor X on species D Human Adenovirus Uptake and Transduction". Viruses 15, n.º 1 (24 de dezembro de 2022): 55. http://dx.doi.org/10.3390/v15010055.
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More than 100 human adenovirus (Ad) types were identified, of which species D comprises the largest group. Heparan sulfate proteoglycans (HSPGs) were shown to function as cell surface receptors for cell binding and uptake of some Ads, but a systematic analysis of species D Ads is lacking. Previous research focused on Ad5 and blood coagulation factor X (FX) complexes, which revealed that Ad5 can transduce cells with low expression levels of its main coxsackievirus-adenovirus receptor in the presence of high HSPG expression levels in a FX dependent manner. Based on our reporter gene-tagged Ad-library, we explored for the first time a broad spectrum of species D Ads to study the role of HSPG on their cellular uptake. This study was performed on three Chinese Hamster Ovary (CHO) cell lines with different forms of HSPG (only proteoglycan (745), non-sulfated HSPG (606) or sulfated HSPG (K1)). The effect of Ad:FX complexes on Ad uptake was explored in the presence of physiological levels of FX in blood (6–10 µg/mL). We found that sulfation of HSPG plays an important role in cellular uptake and transduction of FX-bound Ad5 but neither HSPG nor FX influenced uptake of all tested species D Ads. Because FX has no influence on transduction efficiencies of species D Ads and therefore may not bind to them, these Ads may not be protected from attack by neutralizing IgM antibodies or the complement pathway, which may have implications for species D Ads used as vaccine and gene therapy vectors.
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Váncza, Lórand, Péter Tátrai, Andrea Reszegi, Kornélia Baghy e Ilona Kovalszky. "SPOCK1 with unexpected function. The start of a new career". American Journal of Physiology-Cell Physiology 322, n.º 4 (1 de abril de 2022): C688—C693. http://dx.doi.org/10.1152/ajpcell.00033.2022.
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SPOCK1, 2, and 3 are considered matricellular proteoglycans without a structural role. Their functions are only partly elucidated. SPOCK1 was detected in the brain as a member of the neural synapses, then in the neuromuscular junctions. It plays a role in the regulation of the blood-brain barrier. Its best-characterized activity was its oncogenic potential discovered in 2012. Its deleterious effect on tumor progression was detected on 36 different types of tumors by the end of 2020. However, its mode of action is still not completely understood. Furthermore, even less was discovered about its physiological function. The fact that it was found to localize in the mitochondria and interfered with the lipid metabolism indicated that the full discovery of SPOCK1 is still waiting for us.
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Al-Jamal, Rehab, e Mara S. Ludwig. "Changes in proteoglycans and lung tissue mechanics during excessive mechanical ventilation in rats". American Journal of Physiology-Lung Cellular and Molecular Physiology 281, n.º 5 (1 de novembro de 2001): L1078—L1087. http://dx.doi.org/10.1152/ajplung.2001.281.5.l1078.
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Excessive mechanical ventilation results in changes in lung tissue mechanics. We hypothesized that changes in tissue properties might be related to changes in the extracellular matrix component proteoglycans (PGs). The effect of different ventilation regimens on lung tissue mechanics and PGs was examined in an in vivo rat model. Animals were anesthetized, tracheostomized, and ventilated at a tidal volume of 8 (Vt 8), 20, or 30 (Vt 30) ml/kg, positive end-expiratory pressure of 0 (PEEP0) or 1.5 (PEEP1.5) cmH2O, and frequency of 1.5 Hz for 2 h. The constant-phase model was used to derive airway resistance, tissue elastance, and tissue damping. After physiological measurements, one lung was frozen for immunohistochemistry and the other was reserved for PG extraction and Western blotting. After 2 h of mechanical ventilation, tissue elastance and damping were significantly increased in rats ventilated at Vt 30PEEP0 compared with control rats (ventilated at Vt 8PEEP1.5). Versican, basement membrane heparan sulfate PG, and biglycan were all increased in rat lungs ventilated at Vt 30PEEP0 compared with control rats. At Vt 30PEEP0, heparan sulfate PG and versican staining became prominent in the alveolar wall and airspace; biglycan was mostly localized in the airway wall. These data demonstrate that alterations in lung tissue mechanics with excessive mechanical ventilation are accompanied by changes in all classes of extracellular matrix PG.
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Valentim da Silva, Rodrigo Marcel, Priscila Arend Barichello, Melyssa Lima Medeiros, Waléria Cristina Miranda de Mendonça, Jung Siung Camel Dantas, Oscar Ariel Ronzio, Patricia Meyer Froes e Hassan Galadari. "Effect of Capacitive Radiofrequency on the Fibrosis of Patients with Cellulite". Dermatology Research and Practice 2013 (2013): 1–6. http://dx.doi.org/10.1155/2013/715829.
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Background. Cellulite is a type of lipodystrophy that develops primarily from an alteration in blood circulation or of the lymphatic system that causes structural changes in subcutaneous adipose tissue, collagen, and adjacent proteoglycans. The radiofrequency devices used for cutaneous applications have shown different physiological treatment effects, but there is controversy about the suitable parameters for this type of treatment.Objectives. The aim of this study was to evaluate the effects of low-temperature radiofrequency to confirm the thinning of the collagen tissue and interlobular septa and consequent improvement of cellulite.Methods. A sample of eight women was used to collect ultrasonographic data with a 12 MHz probe that measured collagen fiber thickness. The Vip Electromedicina (Argentina) device, frequency of 0.55 MHz and active electrode 3.5 cm in diameter (area = 9.61 cm2), was applied to a 10 cm2region of the gluteal region for 2 minutes per area of active electrode, during 10 biweekly sessions.Results. The Wilcoxon matched paired test was applied using GraphPad InStat 3.01 for Win95-NT software. Pre- and posttreatment mean collagen fiber thickness showed a 24.66% reduction from 1.01 to 0.67 mm. Statistical analysis using the Wilcoxon matched paired test obtained a significant two-tailedPvalue of 0.0391.Conclusion. It was concluded that the use of more comfortable temperatures favored a reduction in fibrous septum thickness and consequent cellulite improvement, evidenced by the lower degree of severity and decrease in interlobular septal thickness.
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Gilbert, Sophie Jane, Cleo Selina Bonnet e Emma Jane Blain. "Mechanical Cues: Bidirectional Reciprocity in the Extracellular Matrix Drives Mechano-Signalling in Articular Cartilage". International Journal of Molecular Sciences 22, n.º 24 (18 de dezembro de 2021): 13595. http://dx.doi.org/10.3390/ijms222413595.
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The composition and organisation of the extracellular matrix (ECM), particularly the pericellular matrix (PCM), in articular cartilage is critical to its biomechanical functionality; the presence of proteoglycans such as aggrecan, entrapped within a type II collagen fibrillar network, confers mechanical resilience underweight-bearing. Furthermore, components of the PCM including type VI collagen, perlecan, small leucine-rich proteoglycans—decorin and biglycan—and fibronectin facilitate the transduction of both biomechanical and biochemical signals to the residing chondrocytes, thereby regulating the process of mechanotransduction in cartilage. In this review, we summarise the literature reporting on the bidirectional reciprocity of the ECM in chondrocyte mechano-signalling and articular cartilage homeostasis. Specifically, we discuss studies that have characterised the response of articular cartilage to mechanical perturbations in the local tissue environment and how the magnitude or type of loading applied elicits cellular behaviours to effect change. In vivo, including transgenic approaches, and in vitro studies have illustrated how physiological loading maintains a homeostatic balance of anabolic and catabolic activities, involving the direct engagement of many PCM molecules in orchestrating this slow but consistent turnover of the cartilage matrix. Furthermore, we document studies characterising how abnormal, non-physiological loading including excessive loading or joint trauma negatively impacts matrix molecule biosynthesis and/or organisation, affecting PCM mechanical properties and reducing the tissue’s ability to withstand load. We present compelling evidence showing that reciprocal engagement of the cells with this altered ECM environment can thus impact tissue homeostasis and, if sustained, can result in cartilage degradation and onset of osteoarthritis pathology. Enhanced dysregulation of PCM/ECM turnover is partially driven by mechanically mediated proteolytic degradation of cartilage ECM components. This generates bioactive breakdown fragments such as fibronectin, biglycan and lumican fragments, which can subsequently activate or inhibit additional signalling pathways including those involved in inflammation. Finally, we discuss how bidirectionality within the ECM is critically important in enabling the chondrocytes to synthesise and release PCM/ECM molecules, growth factors, pro-inflammatory cytokines and proteolytic enzymes, under a specified load, to influence PCM/ECM composition and mechanical properties in cartilage health and disease.
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Alter, S. C., D. D. Metcalfe, T. R. Bradford e L. B. Schwartz. "Regulation of human mast cell tryptase. Effects of enzyme concentration, ionic strength and the structure and negative charge density of polysaccharides". Biochemical Journal 248, n.º 3 (15 de dezembro de 1987): 821–27. http://dx.doi.org/10.1042/bj2480821.
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Tryptase was previously shown to undergo rapid inactivation under physiological conditions unless stabilized by the presence of heparin. The current study shows that increasing the concentration of free tryptase enhances the preservation of enzymic activity, consistent with dissociation of the tetramer, rather than autodegradation, as the mechanism of inactivation. Heparin glycosaminoglycan fragments of Mr greater than 5700 are necessary for complete stabilization of tryptase activity. This stabilizing effect depends upon negative charge density rather than carbohydrate composition. Thus, keratan sulphate or hyaluronic acid were no better than physiological buffer alone; chondroitin monosulphates and heparan sulphate each prolonged the t1/2 about 20-fold over buffer alone; chondroitin sulphate E prolonged the t1/2 69-fold; and dextran sulphate and heparin provided complete stabilization of tryptase activity for 120 min. Poly-D-glutamic acid prolonged the t1/2 55-fold. In each case the loss of tryptase activity followed apparent first-order kinetics. Increasing the NaCl concentration from 0.01 M to 1.0 M increased the stability of free tryptase. In contrast, increasing the NaCl concentration in the presence of stabilizing polysaccharides decreased the stability of tryptase until dissociation of tryptase from each polysaccharide presumably occurred; thereafter tryptase stability increased as did that of free tryptase. The effect of salt concentration on heparin-stabilized tryptase activity (as opposed to stability) was also evaluated. The mast cell proteoglycans heparin and chondroitin sulphate E, by virtue of containing the naturally occurring glycosaminoglycans of highest negative charge density, may play a major role in the regulation of mast cell tryptase activity in vivo.
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Lee, Young Hun, Jun Hyoung Park, Dong Huey Cheon, Taeyoung Kim, Yae Eun Park, Eok-Soo Oh, Ji Eun Lee e Seung-Taek Lee. "Processing of syndecan-2 by matrix metalloproteinase-14 and effect of its cleavage on VEGF-induced tube formation of HUVECs". Biochemical Journal 474, n.º 22 (1 de novembro de 2017): 3719–32. http://dx.doi.org/10.1042/bcj20170340.
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Syndecans (SDCs) are transmembrane proteoglycans that are involved in cell adhesion and cell communication. Specifically, SDC2 plays a key role in tumorigenesis, metastasis, and angiogenesis. Previously, we found that rat SDC2 is shed by matrix metalloproteinase-7 (MMP-7) in colon cancer cells. Here, we analyzed the susceptibility of rat SDC2 to various MMPs. We found that the rat SDC2 ectodomain (ECD) fused to the C-terminal Fc region, which was expressed in mammalian cells, was cleaved more efficiently by MMP-14 than MMP-7. Likewise, when anchored on the surface of HeLa cells, rat SDC2 was cleaved more efficiently by the treatment of MMP-14 than MMP-7 and was shed more readily by membrane-anchored MMP-14 than soluble MMP-14. Furthermore, MMP-14 cleaved recombinant SDC2-ECD expressed in Escherichia coli into multiple fragments. Using N-terminal amino acid sequencing and the top-down proteomics approach, we determined that the major cleavage sites were S88↓L89, T98↓M99, T100↓L101, D132↓P133, and N148↓L149 for rat SDC2-ECD and S55↓G56, S65↓P66, P75↓K76, N92↓I93 D122↓P123, and S138↓L139 for human SDC2-ECD. Finally, the rat and human SDC2-ECD lost the ability to suppress vascular endothelial growth factor-induced formation of capillary-like tubes by human umbilical vein endothelial cells following cleavage by MMP-14, but its major cleavage-site mutant of rat SDC2-ECD did not. These results suggest that MMP-14 is a novel enzyme responsible for degrading SDC2 and impairing its physiological roles including angiogenesis.
Teses / dissertações sobre o assunto "Proteoglycans Physiological effect"
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陳智恆 e Chi-hang Chan. "A study of the physiological roles of proteoglycans in the inflammatory bronchial environment of patients with bronchiectasis". Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2003. http://hub.hku.hk/bib/B30408751.
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De, Angelis Daniel. "Syndecan-1 expression during postnatal tooth and oral mucosa development in 2 day to 6 week old rats". Title page, contents and abstract only, 2000. http://web4.library.adelaide.edu.au/theses/09DM/09dmd284.pdf.
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Includes bibliographical references (leaves 68-76) Aims to observe changes in the expression of syndecan-1 in both the developing epithelium of the rat oral mucosa, and in epithelial cell rests of Malassez in the developing periodontium of normal rat molars, from late crown development through to early eruption.
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Chai, Lin. "Proteoglycans in the inner limiting membrane and their influence on axonal behavior in embryonic chicken retina". Thesis, 1993. http://hdl.handle.net/1957/36250.
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Shi, Lei. "On the Mechanical Experiments and Modeling of Human Cervix". Thesis, 2021. https://doi.org/10.7916/d8-eaga-g814.
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The mechanical function of the uterine cervix is critical for a healthy pregnancy. During pregnancy, the cervix undergoes a significant remodeling from a mechanical barrier into a compliant structure to allow for a successful delivery. A too early or too late cervical softening will lead to spontaneous preterm births (sPTB) or dystocia. PTB is a leading cause of neonatal death, affecting 15 million newly born babies each year around the world. According to CDC, the rate of PTB increases in recent years. Dystocia increases the risk to both mother and newborn babies, leading to neonatal asphyxia, neonatal infection, uterine rupture, or other dangerous sequelae. Therefore, it is significant to have a better correlation of the mechanical properties change and the biological remodeling process of the cervix during pregnancy. This thesis will focus on (1) mechanical experiments of the human cervix, and (2) the development of a material constitutive model for cervix to characterize the complex microstructure-related mechanical property of the cervix.
In this thesis, a spherical indentation test was designed and conducted on human cervical samples sliced perpendicular to the axial direction, to characterize the compressive mechanical behavior of the human cervix. A uniaxial tensile was designed and conducted on the strip samples cut along and perpendicular to the preferential fiber direction from the indentation samples, to characterize the tensile mechanical behavior of the cervix. Based on the detailed experimental investigation, a nonlinear time-dependent anisotropic microstructure-inspired constitutive model has been developed. The basic idea of the model is that the mechanical behavior of the human cervix can be decomposed into an equilibrium and a time-dependent part, and the tension and compression mechanical behaviors are caused by disparate mechanisms. Specifically, the collagen fibrous network plays a major role in the tensile mechanical response, while proteoglycans (PGs), glycosaminoglycans (PGs),, and liquid cause the compressive mechanical response. The tensile time-dependent mechanical behavior of the human cervix is mostly attributed to the interactions between the collagen fiber and other components, while the compressive time-dependent mechanical behavior is mainly attributed to the porous effect. The equilibrium and time-dependent mechanical responses have been well captured using the model, and the results reveal the connection between the ECM microstructure remodeling and mechanical properties change during pregnancy.
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De, Angelis Daniel. "Syndecan-1 expression during postnatal tooth and oral mucosa development in 2 day to 6 week old rats". Thesis, 2000. http://hdl.handle.net/2440/110399.
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Aims to observe changes in the expression of syndecan-1 in both the developing epithelium of the rat oral mucosa, and in epithelial cell rests of Malassez in the developing periodontium of normal rat molars, from late crown development through to early eruption.Thesis (M.D.S.) -- University of Adelaide, School of Dentistry, 2001
Livros sobre o assunto "Proteoglycans Physiological effect"
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David, Evered, Whelan Julie e Symposium on Functions of the Proteoglycans (1986 : Ciba Foundation), eds. Functions of the proteoglycans. Chichester: Wiley, 1986.
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The role of proteoglycans and glycosaminolglycans in aging. Basel: Karger, 1994.
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Chai, Lin. Proteoglycans in the inner limiting membrane and their influence on axonal behavior in embryonic chicken retina. 1993.
Encontre o texto completo da fonteTrabalhos de conferências sobre o assunto "Proteoglycans Physiological effect"
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Seror, Jasmine, Nir Kampf, Alice Maroudas e Jacob Klein. "Nanotribological Investigation of the Role of Proteoglycans in Biolubrication". In ASME 2008 9th Biennial Conference on Engineering Systems Design and Analysis. ASMEDC, 2008. http://dx.doi.org/10.1115/esda2008-59390.
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Articular joints in human body are uniquely efficient lubrication systems. While the cartilage surfaces slide past each other under physiological working conditions (pressure of tens of atmospheres and shear rates up to 106 – 107 Hz), the friction coefficient (μ) achieves extremely low values (down to 0.001) never successfully reached by mechanical prosthetic devices. Friction studies on polymer brushes attached to surfaces have recently demonstrated (17) their ability to reduce friction between the rubbing surfaces to extremely low values by means of the hydrated ions and the charges on the polymer chains. We propose that the extremely efficient lubrication observed in living joints arises from the presence of a brush-like phase of charged macromolecules at the surface of the cartilage superficial zone: hydration layers which surround the charges on the cartilage macromolecules might provide a lubricating ball-bearing-like effect as demonstrated for the synthetic polyelectrolytes (17). In this work macromolecules of the cartilage superficial zone (aggrecans) are extracted from human femoral heads and purified using well developed biochemical techniques (20). The extracted molecules are then characterized with atomic force microscope (AFM). By means of a surface force balance (SFB) normal and shear interactions between mica surfaces coated with these molecules are examined focusing on the frictional forces between such surfaces at normal stresses similar to those in human joints.
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Huyghe, J. M., C. J. M. Jongeneelen, F. Kraaijeveld e Y. Schroeder. "3D Finite Strains in Bovine Annulus Fibrosus Tissue". In ASME 2007 Summer Bioengineering Conference. American Society of Mechanical Engineers, 2007. http://dx.doi.org/10.1115/sbc2007-176508.
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Intervertebral disc tissue consists of a fluid-filled extra-cellular matrix, in which living cells are sparsely dispersed. The mechanical function is highly dependent on the composition of the extra-cellular matrix, which primary consists of collagen fibrils and negatively charged proteoglycans. Due to the fixed charges of the proteoglycans (PG’s), the cation concentration inside the tissue is higher than physiological. This excess of ion particles leads to an osmotic pressure difference, which causes swelling of the tissue [1]. Because the intervertebral disc is gripped between two vertebrae, the swelling is constrained in vivo, resulting in a intradiscal pressure of 0.1 to 0.2 MPa in supine position. It has been shown that the osmotic pressure inside cartilaginous tissues is much higher than would be expected based on its FCD [2]. This is because part of the water in the tissue is absorbed by the collagen fibers. The proteoglycan molecules, because of their large size, are excluded from this intra-fibrillar space. This means that their effective concentrations are much higher in the extra-fibrillar space than if they were distributed uniformly throughout the entire matrix. Hence, the effective fixed charge density is higher than if computed from total tissue water content. A recent study demonstrates that intrafibrillar water increases osmolarity within the annulus fibrosus substantially [3]. On the other hand, Wognum et al. [4] showed by means of a physical and a numerical model of the disc that high osmolarity within the disc has a protective effect against crack propagation within the disc. Hence, the decrease in osmolarity associated with degeneration may be an explanation of (1) the growing number of cracks observed in the degenerating disc as well as (2) the poor correlation between external loading and crack propagation [5]. The purpose of the present study is to test the hypothesis of Wognum et al. [4] through direct observation of the deformation of annulus fibrosus tissue around discontinuities within its collagen network.
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Rahimi, Abdolrasol, e Hamed Hatami-Marbini. "Hydration Effects on Tensile Properties of the Corneal Stroma". In ASME 2013 Summer Bioengineering Conference. American Society of Mechanical Engineers, 2013. http://dx.doi.org/10.1115/sbc2013-14788.
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The mechanical behavior of the cornea is mainly governed by the microstructure and composition of the stroma. The stroma is a highly ordered extracellular matrix and constitutes about 90% of the corneal thickness. From the mechanics point of view, the corneal stroma can be considered as a polyelectrolyte gel which is composed of collagen fibrils embedded in an aqueous matrix. The collagen fibrils compose about 70% of cornea’s dry mass and are arranged in a regular lattice structure [2]. Previous studies have shown that while the collagen fibrils are primarily located parallel to the surface, they are not distributed uniformly in all directions and their preferred orientation is not same in different species. For example, collagen fibrils are almost equally distributed in the nasal-temporal and inferior-superior directions in healthy human corneas [4] and they are mainly aligned in the inferior-superior direction in bovine corneas[2]. The differences in the orientations of the collagen fibrils have seen to have important implications on the mechanical properties of the cornea. In addition to this observation, the relative distance between the collagen fibrils is expected to play a role in defining the mechanics of the tissue. It is well-documented that the proteoglycans bind collagen fibrils at regular sites and control their relative position. The main proteoglycan in the corneal stroma is decorin. Decorin is the simplest small leucine-rich proteoglycan with a single glycosaminoglycan side chain. Chondroitin sulfate, dermatan sulfate, and keratan sulfate are among the prevalent glycosaminoglycans found in the cornea. Under physiological conditions, these linear carbohydrate polymers are ionized and carry negative charges. Therefore, a hydrated gel is formed in the empty space between collagen fibrils by attracting water. It is known that the interaction of these negatively charged glycosaminoglycans with themselves and with the free ions contribute to the corneal swelling pressure and subsequently to its compressive stiffness. Nevertheless, their possible influence on the corneal tensile properties is yet to be determined. In this work, we experimentally characterized the tensile properties of the bovine corneal stroma in different bathing solutions. Furthermore, a quasi-linear viscoelastic (QLV) model was used to examine the effect of bathing fluids and corneal hydration on mechanical parameter of the cornea.
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Mochizuki, Shota, Shun Yanagida e Hiromichi Fujie. "Effect of Enzymatic Degeneration on the Frictonal Property of Articular Cartilage". In ASME 2013 Summer Bioengineering Conference. American Society of Mechanical Engineers, 2013. http://dx.doi.org/10.1115/sbc2013-14461.
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Articular cartilage is consisted of the chondrocyte, collagen fibers and proteoglycan, and interstitial fluid. Basalo et al reported that the coefficient of friction of bovine articular cartilage on a glass surface measured in unconfined compression fashion was increased by the degeneration of proteoglycan [1]. In their friction test, it was difficult to test a small cartilage sample having undulation while the loaded area in cartilage specimen was almost unchanged during friction. For the assessment of frictional properties of enzymatically degenerated cartilage in more physiological condition, we developed a friction tester that allows for performing friction tests of articular cartilage surface against a spherical indenter. With the tester, the loaded area in cartilage specimen translated along with frictional motion while the compressive stress exceeded more than 1 MPa. In the present study, the effect of enzymatic degeneration of proteoglycan and collagen fiber on property of articular cartilage using the friction tester.
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Hussain, Mozammil, Raghu N. Natarajan, Gunnar B. J. Andersson e Howard S. An. "Effect of a Degenerated C5-C6 Disc on the Biomechanics of Adjacent Levels: A Poroelastic Finite Element Investigation". In ASME 2007 Summer Bioengineering Conference. American Society of Mechanical Engineers, 2007. http://dx.doi.org/10.1115/sbc2007-176621.
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Degenerative changes in the cervical spine due to aging are very common causes of neck pain in general population. Although many investigators have quantified the gross morphological changes in the disc with progressive degeneration, the biomechanical changes due to degenerative pathologies of the disc and its effect on the adjacent levels are not well understood. Despite many in vivo and in vitro techniques used to study such complex phenomena, the finite element (FE) method is still a powerful tool to investigate the internal mechanics and complex clinical situations under various physiological loadings particularly when large numbers of parameters are involved. The objective of the present study was to develop and validate a poroelastic FE model of a healthy C3-T1 segment of the cervical spine under physiologic moment loads. The model included the regional effect of change in the fixed charged density of proteoglycan concentration and change in the permeability and porosity due to change in the axial strain of disc tissues. The model was further modified to include various degrees of disc degeneration at the C5-C6 level. Outcomes of this study provided a better understanding on the progression of degeneration along the cervical spine by investigating the biomechanical response of the adjacent segments with an intermediate degenerated C5-C6 level.
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Killian, Megan L., e Tammy L. Haut Donahue. "Effect of Pathological and Physiological Loads on Interleukin-1α Protein Production in Porcine Menisci". In ASME 2008 Summer Bioengineering Conference. American Society of Mechanical Engineers, 2008. http://dx.doi.org/10.1115/sbc2008-192145.
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The meniscus performs several functions for the maintenance of knee joint health, such as load transmission and joint stability. Meniscal lesions have been suggested as a precursor to the onset of osteoarthritis (OA)[1]. Such lesions often lead to surgical removal of the torn portion of the meniscus, increasing cartilage to cartilage contact area. Partial meniscectomies have been shown using finite element analysis and histology to lead to altered and increased mechanical loading on the remaining meniscus and underlying articular cartilage[2,3]. Consequently, pathological compressive strains of more than 15% have been shown to increase proteoglycan breakdown and meniscal matrix degradation[4]. Preliminary investigations in our laboratory have demonstrated an increase in interleukin-1α (IL-1α) gene expression of meniscal explants subjected to pathological levels of dynamic compressive strain [6,7]. This inflammatory cytokine has been attributed to apoptosis and matrix degradation[5]. However, gene expression measurements merely suggest possible matrix remodeling mechanisms and do not necessarily result in protein syntheses from which matrix changes occur. Therefore, the purpose of this study was to quantify protein synthesis of IL-1α in porcine meniscal implants after compressive strain exercises. It was hypothesized that, similar to mRNA expression, protein synthesis for pathologically loaded (0 or 20% dynamic strain) samples would be greater than samples loaded to physiological levels (10% strain).
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Patel, Nisha S., e Alisa Morss Clyne. "A Computational Model of Fibroblast Growth Factor-2 Binding to Isolated and Intact Cell Surface Receptors: Effects of Fibroblast Growth Factor-2 Concentration, Flow and Delivery Mode". In ASME 2012 Summer Bioengineering Conference. American Society of Mechanical Engineers, 2012. http://dx.doi.org/10.1115/sbc2012-80798.
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Fibroblast growth factor-2 (FGF2) plays an important role in both healthy vascular cell functions and pathogenesis in cancer, atherosclerosis and reduced perfusion in diabetes (1–4). FGF2 therapy and targeted drug delivery have great potential in the treatment of such diseases, but have had little clinical success. FGF2 binding kinetics to heparan sulfate proteoglycan (HSPG) and fibroblast growth factor receptors (FGFR) have been largely studied under static conditions (5), however FGF2 binding to endothelial cells occurs physiologically under fluid flow conditions. Understanding complex FGF2 binding kinetics would enable the development of new anti- and pro-angiogenic therapeutics. We developed a computational model of FGF2 binding to FGFR and HSPG with flow to investigate the effect of fluid flow and FGF2 delivery mode on FGF2 binding to isolated or combined binding sites.
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Kasra, Mehran, Vijay Goel, James Martin, Shea-Tien Wang, Woosung Choi e Joseph Buckwalter. "Effects of Hydrostatic Loading Amplitude and Frequency on Rabbit Disc Nucleus Cells". In ASME 2001 International Mechanical Engineering Congress and Exposition. American Society of Mechanical Engineers, 2001. http://dx.doi.org/10.1115/imece2001/bed-23146.
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Abstract Long-term occupational exposure to whole-body vibration increases the risk of disc degeneration and the consequent back pain [1]. The pathogenesis of vibration induced disorders is still not completely clear and there is no effective treatment. Although the potential effects of vibrational stress on extracellular matrix (ECM) assembly and degradation are particularly relevant to the clinical findings of the vibration induced disorders, the effects of vibrational loads on disc cells are largely unknown. It has been shown that hydrostatic pressure directly affects the synthesis of collagen and proteoglycan by the intervertebral disc cells [2–5]. However, these studies investigated only the extent of the effect of quasi-static hydrostatic loads. During daily occupational activities intervertebral disc is exposed to dynamic oscillatory hydrostatic loads, characterized by wide frequency spectrum and variable amplitude. In this case, a physiologic level of amplitude and frequency of hydrostatic pressure may be essential for maintaining the matrix of the disc, while an abnormal amplitude and frequency of hydrostatic pressure may accelerate disc degeneration. The ranges of good and bad loading frequencies and amplitudes still need to be discovered. The objective of this study was to find which of loading frequency and loading amplitude has more influence in affecting disc cell response to vibration. To address this issue we developed a mechanically-active culture system capable of delivering a wide range of loading frequency and amplitude of hydrostatic pressure to cultures of nucleus pulposus cells. We used nucleus cells, which are exposed mainly to hydrostatic loading in vivo.
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Sampat, Sonal R., Drew A. Robinson, George P. Ackerman, Matthew V. Dermksian, Gerard A. Ateshian e Clark T. Hung. "Applied Osmotic Loading for Promoting Development of Engineered Cartilage". In ASME 2012 Summer Bioengineering Conference. American Society of Mechanical Engineers, 2012. http://dx.doi.org/10.1115/sbc2012-80449.
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The avascular nature of cartilage and the harsh joint loading environment lead to a poor intrinsic healing capacity after injury, motivating the development of cell-based therapies for repair. Synovium-derived stem cells (SDSCs) have the potential for differentiating down a chondrogenic lineage and are thought to aid in articular cartilage repair after damage in vivo1. In the present study, we adopt a two-pronged strategy for growing clinically relevant cartilage grafts. Firstly, we compare the potential of SDSCs versus chondrocytes for engineering functional constructs. Secondly, we investigate the effect of extracellular osmolarity on mechanical and biochemical properties of SDSCs and similarly passaged chondrocytes in 3D culture. This approach is motivated by the fact that the in situ osmotic environment of chondrocytes varies with proteoglycan content and tissue deformation, altering the regulation of chondrocyte activity through mechanotransduction pathways2. We test the hypothesis that application of a hypertonic, more physiologic osmotic environment (created by addition of NaCl and KCl) relative to hypotonic media (300 mOsm), during 3D culture of SDSCs or chondrocytes in agarose hydrogels, improves the biochemical composition and mechanical properties of engineered tissue constructs.
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Nguyen, Thao D., Reese E. Jones e Brad L. Boyce. "Modeling the Finite Deformation Anisotropic Viscoelastic Behavior of the Cornea". In ASME 2008 Summer Bioengineering Conference. American Society of Mechanical Engineers, 2008. http://dx.doi.org/10.1115/sbc2008-192916.
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This paper presents the development of a finite element model for the cornea as a first step towards a physiologically based model to study the role of cornea and sclera biomechanics in glaucoma. We developed a finite-deformation anisotropic constitutive model of the cornea that considers the effects of the fibrilar microstructure on the viscoelastic stress response. The model was base on the hypothesis that the dominant mechanism for the tensile viscoelastic behavior of the cornea is the viscoelastic stretching of the collagen lamellae. This approach yielded two main results. First, the viscoelastic properties of the cornea are derivable directly from the viscoelastic properties of the collagen fibrils and proteoglycan matrix. Second, the anisotropy in the stress response and creep response are determined solely by the arrangement collagen lamellae, which depends on orientation and material position. This allows the model parameters that determines anisotropy to be obtained from microstructural characterizations, such as the X-ray diffraction experiments of Meek and coworkers [1], while the model parameters that determines viscoelasticity to be determined from mechanical experiments. For this initial work, the viscoelastic parameters were fitted to the uniaxial tensile strip tests [2] and inflation tests with digital image correlation (DIC) [3] of bovine cornea performed by our group. Since microstructural characterizations are not available for bovine cornea, we used the data of Aghamohammadzadeh et. al. [1] for the human cornea.